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Articular Cartilage Regeneration in Veterinary Medicine

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Cell Biology and Translational Medicine, Volume 17

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1401))

Abstract

Cartilage is an avascular tissue with a limited rate of oxygen and nutrient diffusion, resulting in its inability to heal spontaneously. Articular cartilage defects eventually lead to osteoarthritis (OA), the endpoint of progressive destruction of cartilage. In companion animals, OA is the most common joint disease, and many pain management and surgical attempts have been made to find an appropriate treatment. Pain management of OA is usually the first choice of OA therapy, which is often managed with nonsteroidal anti-inflammatory drugs (NSAIDs). To avoid known negative side effects of NSAIDs, other approaches are being considered, such as the use of anti-nerve growth factor monoclonal antibodies (anti-NGF mAB), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs). The latter is increasingly being recognized as effective in reducing or even eliminating pain and lameness associated with OA. However, the in vivo mechanisms of MSC action do not relate to their differentiation potential, but rather to their immunomodulatory functions. Achieving actual regeneration of cartilage to prevent OA from developing or even revert already existing OA condition has not yet been achieved. Several techniques have been tried to overcome cartilage’s inability to regenerate, from osteochondral transplantation, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). Combinatory use of MSCs unique features and biomaterials is also being investigated with the aim to as much as possible recapitulate the native microenvironment of the cartilage, yet so far none of the methods have produced reliable and truly effective results. Although OA, for now, remains an incurable disease, novel techniques are being developed, rendering hope for the future accomplishment of actual cartilage regeneration. The aim of this chapter is firstly to summarize known and developing pain management options for OA, secondly to present surgical attempts to regenerate articular cartilage, and finally to present the attempts to improve existing regenerative treatment options using mesenchymal stem cells, with the vision for the possible use of developing strategies in veterinary medicine.

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Abbreviations

ACI:

Autologous chondrocyte implantation

Anti-NGF mAB:

Anti-nerve growth factor monoclonal antibodies

BMP2:

Bone morphogenetic protein-2

CD105:

Cluster of differentiation 105

CD73:

Cluster of differentiation 73

CD90:

Cluster of differentiation 90

CD45:

Cluster of differentiation 45

CD34:

Cluster of differentiation 34

CD14:

Cluster of differentiation 14

CD11b:

Cluster of differentiation 11b

CD79a:

Cluster of differentiation 79a

CD19:

Cluster of differentiation 19

COMP:

Cartilage oligomeric matrix protein

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

FGF:

Fibroblast growth factor

GAGs:

Glycosaminoglycans

HA:

Hyaluronic acid

HIF-1α:

Hypoxia-inducible factor-1alpha

HLA:

Human leukocyte antigen

IGF:

Insulin-like growth factor

MACI:

Matrix-induced autologous chondrocyte implantation

MAT-3:

Matrilin-3 protein

MMP13:

Matrix metalloproteinase 13

MMP:

Modified Maquet procedure

MSCs:

Mesenchymal stem cells/medicinal signaling cells

NGF:

Nerve growth factor

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OA:

Osteoarthritis

OCD:

Osteochondritis dissecans

PDGF:

Platelet-derived growth factor

PRP:

Platelet-rich plasma

PCL:

Polycaprolactone

PEG:

Polyethylene glycol

PGA:

Polyglycolic acid

PLA:

Polylactic acid

PLGA:

Polylactic-co-glycolic acid

PTHrP:

Parathyroid hormone-related protein

ROS:

Reactive oxygen species

RUNX2:

Runt-related transcription factor 2

SOX9:

SRY-box transcription factor 9

TGF-β:

Transforming growth factor beta

TPLO:

Tibial plateau leveling osteotomy

TSP-1:

Thrombospondin-1

TTA:

Tibial tuberosity advancement

VEGF:

Vascular endothelial growth factor

2D:

Two-dimensional

3D:

Three-dimensional

References

  • Acosta CA et al (2006) Gene expression and proliferation analysis in young, aged, and osteoarthritic sheep chondrocytes effect of growth factor treatment. J Orthop Res 24(11):2087–2094

    Article  CAS  PubMed  Google Scholar 

  • Ahmed TA, Hincke MT (2010) Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B Rev 16(3):305–329

    Article  CAS  PubMed  Google Scholar 

  • Ahmed MR et al (2014) Combination of ADMSCs and chondrocytes reduces hypertrophy and improves the functional properties of osteoarthritic cartilage. Osteoarthr Cartil 22(11):1894–1901

    Article  CAS  Google Scholar 

  • Altman RD et al (1992) Preliminary observations of chondral abrasion in a canine model. Ann Rheum Dis 51(9):1056–1062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alves JC et al (2020) A pilot study on the efficacy of a single intra-articular administration of triamcinolone acetonide, hyaluronan, and a combination of both for clinical management of osteoarthritis in police working dogs. Front Vet Sci 7:512523

    Article  PubMed  PubMed Central  Google Scholar 

  • Amann E et al (2017) Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures. Acta Biomater 52:130–144

    Article  CAS  PubMed  Google Scholar 

  • An C et al (2010) IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells into chondrocytes-like cells. Ann Biomed Eng 38(4):1647–1654

    Article  PubMed  Google Scholar 

  • Anderson KL et al (2020) Risk factors for canine osteoarthritis and its predisposing arthropathies: a systematic review. Front Vet Sci 7:220

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson-Baron M et al (2020) Suppression of hypertrophy during in vitro chondrogenesis of cocultures of human mesenchymal stem cells and nasal chondrocytes correlates with lack of in vivo calcification and vascular invasion. Front Bioeng Biotechnol 8:572356

    Article  PubMed  Google Scholar 

  • Ando I et al (2016) Changes in serum NGF levels after the exercise load in dogs: a pilot study. J Vet Med Sci 78(11):1709–1712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ando I et al (2020) Evaluation of stress status using the stress map for guide dog candidates in the training stage using variations in the serum cortisol with nerve growth factor and magnesium ions. Vet Anim Sci 10:100129

    Article  PubMed  PubMed Central  Google Scholar 

  • Antoni D et al (2015) Three-dimensional cell culture: a breakthrough in vivo. Int J Mol Sci 16(3):5517–5527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aragon CL, Hofmeister EH, Budsberg SC (2007) Systematic review of clinical trials of treatments for osteoarthritis in dogs. J Am Vet Med Assoc 230(4):514–521

    Article  PubMed  Google Scholar 

  • Arevalo-Turrubiarte M et al (2019) Analysis of mesenchymal cells (MSCs) from bone marrow, synovial fluid and mesenteric, neck and tail adipose tissue sources from equines. Stem Cell Res 37:101442

    Article  CAS  PubMed  Google Scholar 

  • Armiento AR, Alini M, Stoddart MJ (2019) Articular fibrocartilage – why does hyaline cartilage fail to repair? Adv Drug Deliv Rev 146:289–305

    Article  CAS  PubMed  Google Scholar 

  • Barlian A et al (2018) Chondrogenic differentiation of adipose-derived mesenchymal stem cells induced by L-ascorbic acid and platelet rich plasma on silk fibroin scaffold. Peer J 6:e5809

    Article  PubMed  PubMed Central  Google Scholar 

  • Barnewitz D et al (2003) Tissue engineering: new treatment of cartilage alterations in degenerative joint diseases in horses – preliminary results of a long term study. Berl Munch Tierarztl Wochenschr 116(3-4):157–161

    CAS  PubMed  Google Scholar 

  • Bedingfield SK et al (2020) Matrix-targeted nanoparticles for MMP13 RNA interference blocks post-traumatic osteoarthritis. bioRxiv:2020.01.30.925321

    Google Scholar 

  • Bekkers JE et al (2013a) Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Am J Sports Med 41(9):2158–2166

    Article  PubMed  Google Scholar 

  • Bekkers JE et al (2013b) One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats. Osteoarthr Cartil 21(7):950–956

    Article  CAS  Google Scholar 

  • Benninghoff A (1925) Form und Bau der Gelenkknorpel in ihren Beziehungen zur Funktion. Z Zellforsch Mikrosk Anat 2(5):783–862

    Article  Google Scholar 

  • Benoit DS et al (2008) Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater 7(10):816–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertoni L et al (2021) Evaluation of allogeneic bone-marrow-derived and umbilical cord blood-derived mesenchymal stem cells to prevent the development of osteoarthritis in an equine model. Int J Mol Sci 22(5)

    Google Scholar 

  • Bian L et al (2012) Dynamic compressive loading enhances cartilage matrix synthesis and distribution and suppresses hypertrophy in hMSC-laden hyaluronic acid hydrogels. Tissue Eng Part A 18(7-8):715–724

    Article  CAS  PubMed  Google Scholar 

  • Black LL et al (2007) Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 8(4):272–284

    PubMed  Google Scholar 

  • Bodo G et al (2004) Autologous osteochondral grafting (mosaic arthroplasty) for treatment of subchondral cystic lesions in the equine stifle and fetlock joints. Vet Surg 33(6):588–596

    Article  PubMed  Google Scholar 

  • Bora FW Jr, Miller G (1987) Joint physiology, cartilage metabolism, and the etiology of osteoarthritis. Hand Clin 3(3):325–336

    Article  PubMed  Google Scholar 

  • Borochowitz ZU et al (2004) Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD. J Med Genet 41(5):366–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bosnakovski D et al (2004) Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells in pellet cultural system. Exp Hematol 32(5):502–509

    Article  CAS  PubMed  Google Scholar 

  • Bouck GR, Miller CW, Taves CL (1995) A comparison of surgical and medical treatment of fragmented coronoid process and osteochondritis dissecans of the canine elbow. Vet Comp Orthop Traumatol 08(04):177–183

    Article  Google Scholar 

  • Branly T et al (2018) Improvement of the chondrocyte-specific phenotype upon equine bone marrow mesenchymal stem cell differentiation: influence of culture time, transforming growth factors and type I collagen siRNAs on the differentiation index. Int J Mol Sci 19(2)

    Google Scholar 

  • Breinan HA et al (1997) Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model. J Bone Joint Surg Am 79(10):1439–1451

    Article  CAS  PubMed  Google Scholar 

  • Breinan HA et al (2000) Healing of canine articular cartilage defects treated with microfracture, a type-II collagen matrix, or cultured autologous chondrocytes. J Orthop Res 18(5):781–789

    Article  CAS  PubMed  Google Scholar 

  • Brighton CT, Heppenstall RB (1971) Oxygen tension in zones of the epiphyseal plate, the metaphysis and diaphysis. An in vitro and in vivo study in rats and rabbits. J Bone Joint Surg Am 53(4):719–728

    Article  CAS  PubMed  Google Scholar 

  • Brittberg M et al (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895

    Article  CAS  PubMed  Google Scholar 

  • Brondeel C et al (2021) Review: mesenchymal stem cell therapy in canine osteoarthritis research: “Experientia Docet” (Experience will teach us). Front Vet Sci 8:668881

    Article  PubMed  PubMed Central  Google Scholar 

  • Browe DC et al (2019) Hypoxia activates the PTHrP -MEF2C pathway to attenuate hypertrophy in mesenchymal stem cell derived cartilage. Sci Rep 9(1):13274

    Article  PubMed  PubMed Central  Google Scholar 

  • Bruderer M et al (2014) Role and regulation of RUNX2 in osteogenesis. Eur Cell Mater 28:269–286

    Article  CAS  PubMed  Google Scholar 

  • Burks RT et al (2006) The use of a single osteochondral autograft plug in the treatment of a large osteochondral lesion in the femoral condyle: an experimental study in sheep. Am J Sports Med 34(2):247–255

    Article  PubMed  Google Scholar 

  • Cao Z et al (2017) Hypertrophic differentiation of mesenchymal stem cells is suppressed by xanthotoxin via the p38MAPK/HDAC4 pathway. Mol Med Rep 16(3):2740–2746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9(5):641–650

    Article  CAS  PubMed  Google Scholar 

  • Caplan AI (2017) Mesenchymal stem cells: time to change the name! Stem Cells Transl Med 6(6):1445–1451

    Article  PubMed  PubMed Central  Google Scholar 

  • Carrade DD et al (2011) Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses. Cytotherapy 13(4):419–430

    Article  CAS  PubMed  Google Scholar 

  • Catarino J et al (2020) Treatment of canine osteoarthritis with allogeneic platelet-rich plasma: review of five cases. Open Vet J 10(2):226–231

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen S et al (2019) MicroRNA-218 promotes early chondrogenesis of mesenchymal stem cells and inhibits later chondrocyte maturation. BMC Biotechnol 19(1):6

    Article  PubMed  PubMed Central  Google Scholar 

  • Cherubino P et al (2003) Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report. J Orthop Surg (Hong Kong) 11(1):10–15

    Article  CAS  Google Scholar 

  • Chiara G, Ranieri C (2009) Cartilage and bone extracellular matrix. Curr Pharm Des 15(12):1334–1348

    Article  Google Scholar 

  • Cho H, Lee A, Kim K (2018) The effect of serum types on chondrogenic differentiation of adipose-derived stem cells. Biomater Res 22:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi KH et al (2010) The chondrogenic differentiation of mesenchymal stem cells on an extracellular matrix scaffold derived from porcine chondrocytes. Biomaterials 31(20):5355–5365

    Article  CAS  PubMed  Google Scholar 

  • Clarke SP et al (2005) Prevalence of radiographic signs of degenerative joint disease in a hospital population of cats. Vet Rec 157(25):793–799

    Article  CAS  PubMed  Google Scholar 

  • Cohen JM et al (2009) Long-term outcome in 44 horses with stifle lameness after arthroscopic exploration and debridement. Vet Surg 38(4):543–551

    Article  PubMed  Google Scholar 

  • Cook JL, Payne JT (1997) Surgical treatment of osteoarthritis. Vet Clin North Am Small Anim Pract 27(4):931–944

    Article  CAS  PubMed  Google Scholar 

  • Cook JL, Hudson CC, Kuroki K (2008) Autogenous osteochondral grafting for treatment of stifle osteochondrosis in dogs. Vet Surg 37(4):311–321

    Article  PubMed  Google Scholar 

  • Cook JL et al (2014) A novel system improves preservation of osteochondral allografts. Clin Orthop Relat Res 472(11):3404–3414

    Article  PubMed  PubMed Central  Google Scholar 

  • Cook JL et al (2016) Importance of donor chondrocyte viability for osteochondral allografts. Am J Sports Med 44(5):1260–1268

    Article  PubMed  Google Scholar 

  • Cope PJ et al (2019) Models of osteoarthritis: the good, the bad and the promising. Osteoarthr Cartil 27(2):230–239

    Article  CAS  Google Scholar 

  • Cortes I et al (2021) A scaffold- and serum-free method to mimic human stable cartilage validated by secretome. Tissue Eng Part A 27(5-6):311–327

    Article  CAS  PubMed  Google Scholar 

  • Cuervo B et al (2020) Objective comparison between platelet rich plasma alone and in combination with physical therapy in dogs with osteoarthritis caused by hip dysplasia. Animals (Basel) 10(2)

    Google Scholar 

  • Curran JM, Chen R, Hunt JA (2006) The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrate. Biomaterials 27(27):4783–4793

    Article  CAS  PubMed  Google Scholar 

  • De Angelis E et al (2020) Gene expression markers in horse articular chondrocytes: chondrogenic differentiation IN VITRO depends on the proliferative potential and ageing. Implication for tissue engineering of cartilage. Res Vet Sci 128:107–117

    Article  PubMed  Google Scholar 

  • De Armond CC et al (2021) Three-dimensional-printed custom guides for bipolar coxofemoral osteochondral allograft in dogs. PLoS One 16(2):e0244208

    Article  PubMed  PubMed Central  Google Scholar 

  • De Bari C, Dell’Accio F, Luyten FP (2001) Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum 44(1):85–95

    Article  PubMed  Google Scholar 

  • Dell’Accio F et al (2003) Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J Orthop Res 21(1):123–131

    Article  PubMed  Google Scholar 

  • Dennis JE et al (1999) A quadripotential mesenchymal progenitor cell isolated from the marrow of an adult mouse. J Bone Miner Res 14(5):700–709

    Article  CAS  PubMed  Google Scholar 

  • Denys M et al (2020) Biosafety evaluation of equine Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) by systematic pathogen screening in peripheral maternal blood and paired UC-MSCs. Biopreserv Biobank

    Google Scholar 

  • Dew TL, Martin RA (1992) Functional, radiographic, and histologic assessment of healing of autogenous osteochondral grafts and full-thickness cartilage defects in the talus of dogs. Am J Vet Res 53(11):2141–2152

    CAS  PubMed  Google Scholar 

  • Dieppe PA, Lohmander LS (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365(9463):965–973

    Article  CAS  PubMed  Google Scholar 

  • Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  • Dou C et al (2016) Xanthotoxin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis. Osteoporos Int 27(7):2335–2344

    Article  CAS  PubMed  Google Scholar 

  • Dreher SI et al (2020) Significance of MEF2C and RUNX3 regulation for endochondral differentiation of human mesenchymal progenitor cells. Front Cell Dev Biol 8:81

    Article  PubMed  PubMed Central  Google Scholar 

  • Dudakovic A et al (2014) High-resolution molecular validation of self-renewal and spontaneous differentiation in clinical-grade adipose-tissue derived human mesenchymal stem cells. J Cell Biochem 115(10):1816–1828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dyson SJ (2004) Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992–2000). Equine Vet J 36(5):415–419

    Article  CAS  PubMed  Google Scholar 

  • Egger D et al (2019) From 3D to 3D: isolation of mesenchymal stem/stromal cells into a three-dimensional human platelet lysate matrix. Stem Cell Res Ther 10(1):248

    Article  PubMed  PubMed Central  Google Scholar 

  • Enomoto M et al (2019) Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats. Vet Rec 184(1):23

    Article  PubMed  Google Scholar 

  • Familiari F et al (2018) Clinical outcomes and failure rates of osteochondral allograft transplantation in the knee: a systematic review. Am J Sports Med 46(14):3541–3549

    Article  PubMed  Google Scholar 

  • Fan L et al (2012) Vitamin C-reinforcing silk fibroin nanofibrous matrices for skin care application. RCS Adv 2:4110–4119

    Google Scholar 

  • Feng Q et al (2017) Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy. Acta Biomater 53:329–342

    Article  CAS  PubMed  Google Scholar 

  • Ferris DJ et al (2014) Clinical outcome after intra-articular administration of bone marrow derived mesenchymal stem cells in 33 horses with stifle injury. Vet Surg 43(3):255–265

    Article  PubMed  Google Scholar 

  • Fischer J et al (2010) Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis. Arthritis Rheum 62(9):2696–2706

    Article  CAS  PubMed  Google Scholar 

  • Fischer J et al (2014) Intermittent PTHrP(1-34) exposure augments chondrogenesis and reduces hypertrophy of mesenchymal stromal cells. Stem Cells Dev 23(20):2513–2523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzpatrick N, Yeadon R, Smith TJ (2009) Early clinical experience with osteochondral autograft transfer for treatment of osteochondritis dissecans of the medial humeral condyle in dogs. Vet Surg 38(2):246–260

    Article  PubMed  Google Scholar 

  • Fitzpatrick N et al (2010) Osteochondral autograft transfer for treatment of osteochondritis dissecans of the caudocentral humeral head in dogs. Vet Surg 39(8):925–935

    Article  PubMed  Google Scholar 

  • Fitzpatrick N et al (2012) Osteochondral autograft transfer for the treatment of osteochondritis dissecans of the medial femoral condyle in dogs. Vet Comp Orthop Traumatol 25(2):135–143

    Article  CAS  PubMed  Google Scholar 

  • Fortier LA et al (1998) Isolation and chondrocytic differentiation of equine bone marrow-derived mesenchymal stem cells. Am J Vet Res 59(9):1182–1187

    CAS  PubMed  Google Scholar 

  • Foster TE et al (2009) Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 37(11):2259–2272

    Article  PubMed  Google Scholar 

  • Franklin SP, Cook JL (2013) Prospective trial of autologous conditioned plasma versus hyaluronan plus corticosteroid for elbow osteoarthritis in dogs. Can Vet J 54(9):881–884

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franklin SP, Garner BC, Cook JL (2015) Characteristics of canine platelet-rich plasma prepared with five commercially available systems. Am J Vet Res 76(9):822–827

    Article  CAS  PubMed  Google Scholar 

  • Frisbie DD et al (1999) Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses. Vet Surg 28(4):242–255

    Article  CAS  PubMed  Google Scholar 

  • Frisbie DD, Cross MW, McIlwraith CW (2006) A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee. Vet Comp Orthop Traumatol 19(3):142–146

    Article  CAS  PubMed  Google Scholar 

  • Frisbie DD et al (2008) Evaluation of autologous chondrocyte transplantation via a collagen membrane in equine articular defects: results at 12 and 18 months. Osteoarthr Cartil 16(6):667–679

    Article  CAS  Google Scholar 

  • Frisbie DD et al (2009) In vivo evaluation of autologous cartilage fragment-loaded scaffolds implanted into equine articular defects and compared with autologous chondrocyte implantation. Am J Sports Med 37(Suppl 1):71S–80S

    Article  PubMed  Google Scholar 

  • Fujiki M et al (2007) Effects of treatment with polysulfated glycosaminoglycan on serum cartilage oligomeric matrix protein and C-reactive protein concentrations, serum matrix metalloproteinase-2 and -9 activities, and lameness in dogs with osteoarthritis. Am J Vet Res 68(8):827–833

    Article  CAS  PubMed  Google Scholar 

  • Gale AL et al (2019) The effect of hypoxia on chondrogenesis of equine synovial membrane-derived and bone marrow-derived mesenchymal stem cells. BMC Vet Res 15(1):201

    Article  PubMed  PubMed Central  Google Scholar 

  • Gandhimathi C (2015) Controlled release of dexamethasone in PCL/silk fibroin/ascorbic acid nanoparticles for the initiation of adipose derived stem cells into osteogenesis. J Drug Metab Toxicol 6(1):2

    Google Scholar 

  • Ge Z et al (2012) Functional biomaterials for cartilage regeneration. J Biomed Mater Res A 100(9):2526–2536

    PubMed  Google Scholar 

  • Gearing DP et al (2013) A fully caninised anti-NGF monoclonal antibody for pain relief in dogs. BMC Vet Res 9:226

    Article  PubMed  PubMed Central  Google Scholar 

  • Gearing DP et al (2016) In vitro and in vivo characterization of a fully felinized therapeutic anti-nerve growth factor monoclonal antibody for the treatment of pain in cats. J Vet Intern Med 30(4):1129–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gelse K et al (2011) Thrombospondin-1 prevents excessive ossification in cartilage repair tissue induced by osteogenic protein-1. Tissue Eng Part A 17(15-16):2101–2112

    Article  CAS  PubMed  Google Scholar 

  • Gencoglu H et al (2020) Undenatured type II Collagen (UC-II) in Joint health and disease: a review on the current knowledge of companion animals. Animals (Basel) 10(4)

    Google Scholar 

  • Giannoni P et al (2005) Species variability in the differentiation potential of in vitro-expanded articular chondrocytes restricts predictive studies on cartilage repair using animal models. Tissue Eng 11(1-2):237–248

    Article  CAS  PubMed  Google Scholar 

  • Gill TJ, Steadman JR (2004) Bone marrow stimulation techniques: microfracture, drilling, and abrasion. In: Cole BJ, Malek MM (eds) Articular cartilage lesions: a practical guide to assessment and treatment. Springer, New York, pp 63–72

    Chapter  Google Scholar 

  • Giovannini S et al (2010) Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro. Eur Cell Mater 20:245–259

    Article  CAS  PubMed  Google Scholar 

  • Glenn RE Jr et al (2006) Comparison of fresh osteochondral autografts and allografts: a canine model. Am J Sports Med 34(7):1084–1093

    Article  PubMed  Google Scholar 

  • Godwin EE et al (2012) Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J 44(1):25–32

    Article  CAS  PubMed  Google Scholar 

  • Goldman SM, Barabino GA (2016) Hydrodynamic loading in concomitance with exogenous cytokine stimulation modulates differentiation of bovine mesenchymal stem cells towards osteochondral lineages. BMC Biotechnol 16:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Grassel S, Ahmed N (2007) Influence of cellular microenvironment and paracrine signals on chondrogenic differentiation. Front Biosci 12:4946–4956

    Article  CAS  PubMed  Google Scholar 

  • Griffin DJ et al (2015) Mechanical characterization of matrix-induced autologous chondrocyte implantation (MACI(R)) grafts in an equine model at 53 weeks. J Biomech 48(10):1944–1949

    Article  PubMed  Google Scholar 

  • Gruen ME et al (2016) A feline-specific anti-nerve growth factor antibody improves mobility in cats with degenerative joint disease-associated pain: a pilot proof of concept study. J Vet Intern Med 30(4):1138–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guillen-Garcia P et al (2014) Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage 5(2):114–122

    Article  PubMed  PubMed Central  Google Scholar 

  • Guimaraes-Camboa N et al (2017) Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo. Cell Stem Cell 20(3):345–359 e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haddo O et al (2004) The use of chondrogide membrane in autologous chondrocyte implantation. Knee 11(1):51–55

    Article  PubMed  Google Scholar 

  • Handorf AM, Li WJ (2011) Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. PLoS One 6(7):e22887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harman R et al (2016) A prospective, randomized, masked, and placebo-controlled efficacy study of intraarticular allogeneic adipose stem cells for the treatment of osteoarthritis in dogs. Front Vet Sci 3:81

    Article  PubMed  PubMed Central  Google Scholar 

  • Harper TAM (2017a) Femoral head and neck excision. Vet Clin North Am Small Anim Pract 47(4):885–897

    Article  PubMed  Google Scholar 

  • Harper TAM (2017b) INNOPLANT total hip replacement system. Vet Clin North Am Small Anim Pract 47(4):935–944

    Article  PubMed  Google Scholar 

  • Haugh MG et al (2011) Temporal and spatial changes in cartilage-matrix-specific gene expression in mesenchymal stem cells in response to dynamic compression. Tissue Eng Part A 17(23-24):3085–3093

    Article  CAS  PubMed  Google Scholar 

  • Hayes DW Jr, Brower RL, John KJ (2001) Articular cartilage. Anatomy, injury, and repair. Clin Podiatr Med Surg 18(1):35–53

    PubMed  Google Scholar 

  • Hirao M et al (2006) Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. J Biol Chem 281(41):31079–31092

    Article  CAS  PubMed  Google Scholar 

  • Hoshi K et al (2018) Biological aspects of tissue-engineered cartilage. Histochem Cell Biol 149(4):375–381

    Article  CAS  PubMed  Google Scholar 

  • Hu Y et al (2020) A lithium-containing biomaterial promotes chondrogenic differentiation of induced pluripotent stem cells with reducing hypertrophy. Stem Cell Res Ther 11(1):77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang FS et al (2004) Effects of small incongruities in a sheep model of osteochondral autografting. Am J Sports Med 32(8):1842–1848

    Article  PubMed  Google Scholar 

  • Huang AH et al (2010) Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel. Eur Cell Mater 19:72–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J et al (2021) 3D printed gelatin/hydroxyapatite scaffolds for stem cell chondrogenic differentiation and articular cartilage repair. Biomater Sci 9(7):2620–2630

    Article  CAS  PubMed  Google Scholar 

  • Hunziker EB, Stahli A (2008) Surgical suturing of articular cartilage induces osteoarthritis-like changes. Osteoarthr Cartil 16(9):1067–1073

    Article  CAS  Google Scholar 

  • Hurtig M et al (2001) Arthroscopic mosaic arthroplasty in the equine third carpal bone. Vet Surg 30(3):228–239

    Article  CAS  PubMed  Google Scholar 

  • Ibarra C et al (2006) Tissue engineered arthroscopic repair of experimental cartilage lesions in horses (SS-47). Arthroscop J Arthroscop Relat Surg 22(6, Supplement):e24

    Article  Google Scholar 

  • Isola M et al (2011) Nerve growth factor concentrations in the synovial fluid from healthy dogs and dogs with secondary osteoarthritis. Vet Comp Orthop Traumatol 24(4):279–284

    Article  CAS  PubMed  Google Scholar 

  • Janakiramanan N et al (2006) Osteoarthritis cartilage defects: does size matter? Curr Rheumatol Rev 2(4):311–317

    Article  Google Scholar 

  • Jayasuriya CT et al (2012) Matrilin-3 induction of IL-1 receptor antagonist is required for up-regulating collagen II and aggrecan and down-regulating ADAMTS-5 gene expression. Arthritis Res Ther 14(5):R197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen C, Teng Y (2020) Is it time to start transitioning from 2D to 3D cell culture? Front Mol Biosci 7:33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnstone B et al (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238(1):265–272

    Article  CAS  PubMed  Google Scholar 

  • Juhasz T et al (2014) Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures. Cell Signal 26(3):468–482

    Article  CAS  PubMed  Google Scholar 

  • Kang BJ et al (2012) Comparing the osteogenic potential of canine mesenchymal stem cells derived from adipose tissues, bone marrow, umbilical cord blood, and Wharton’s jelly for treating bone defects. J Vet Sci 13(3):299–310

    Article  PubMed  PubMed Central  Google Scholar 

  • Kanichai M et al (2008) Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: a role for AKT and hypoxia-inducible factor (HIF)-1alpha. J Cell Physiol 216(3):708–715

    Article  CAS  PubMed  Google Scholar 

  • Kapusetti G, More N, Choppadandi M (2019) Introduction to ideal characteristics and advanced biomedical applications of biomaterials. In: Paul S (ed) Biomedical engineering and its applications in healthcare. Springer, Singapore, pp 171–204

    Chapter  Google Scholar 

  • Karl A et al (2014) Thyroid hormone-induced hypertrophy in mesenchymal stem cell chondrogenesis is mediated by bone morphogenetic protein-4. Tissue Eng Part A 20(1-2):178–188

    Article  CAS  PubMed  Google Scholar 

  • Kawamoto K et al (1996) Nerve growth factor activity detected in equine peripheral blood of horses with fever after truck transportation. J Equin Sci 7(2):43–46

    Article  Google Scholar 

  • Kendall A et al (2021) Nerve growth factor in the equine joint. Vet J 267:105579

    Article  CAS  PubMed  Google Scholar 

  • Kim SJ et al (2020a) Articular cartilage repair using autologous collagen-induced chondrogenesis (ACIC): a pragmatic and cost-effective enhancement of a traditional technique. Knee Surg Sports Traumatol Arthrosc 28(8):2598–2603

    Article  PubMed  Google Scholar 

  • Kim SA et al (2020b) Atelocollagen promotes chondrogenic differentiation of human adipose-derived mesenchymal stem cells. Sci Rep 10(1):10678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kisiday JD et al (2009) Dynamic compression stimulates proteoglycan synthesis by mesenchymal stem cells in the absence of chondrogenic cytokines. Tissue Eng Part A 15(10):2817–2824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kisiel AH et al (2012) Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum. Am J Vet Res 73(8):1305–1317

    Article  CAS  PubMed  Google Scholar 

  • Koch TG et al (2007) Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol 7:26

    Article  PubMed  PubMed Central  Google Scholar 

  • Kriston-Pal E et al (2020) A regenerative approach to canine osteoarthritis using allogeneic, adipose-derived mesenchymal stem cells. Safety results of a long-term follow-up. Front Vet Sci 7:510

    Article  PubMed  PubMed Central  Google Scholar 

  • Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423(6937):332–336

    Article  CAS  PubMed  Google Scholar 

  • Kundu B et al (2013) Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev 65(4):457–470

    Article  CAS  PubMed  Google Scholar 

  • Lafaver S et al (2007) Tibial tuberosity advancement for stabilization of the canine cranial cruciate ligament-deficient stifle joint: surgical technique, early results, and complications in 101 dogs. Vet Surg 36(6):573–586

    Article  PubMed  Google Scholar 

  • Lane JG et al (2004) Follow-up of osteochondral plug transfers in a goat model: a 6-month study. Am J Sports Med 32(6):1440–1450

    Article  PubMed  Google Scholar 

  • Lascelles BD et al (2015) A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. BMC Vet Res 11:101

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee CR et al (2000) Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee. J Orthop Res 18(5):790–799

    Article  CAS  PubMed  Google Scholar 

  • Lee CR et al (2003) Effects of a cultured autologous chondrocyte-seeded type II collagen scaffold on the healing of a chondral defect in a canine model. J Orthop Res 21(2):272–281

    Article  CAS  PubMed  Google Scholar 

  • Lee J et al (2016) Chondrogenic potential and anti-senescence effect of hypoxia on canine adipose mesenchymal stem cells. Vet Res Commun 40(1):1–10

    Article  CAS  PubMed  Google Scholar 

  • Levorson EJ et al (2014) Cell-derived polymer/extracellular matrix composite scaffolds for cartilage regeneration, Part 2: construct devitalization and determination of chondroinductive capacity. Tissue Eng Part C Methods 20(4):358–372

    Article  CAS  PubMed  Google Scholar 

  • Li J, Pei M (2018) A protocol to prepare decellularized stem cell matrix for rejuvenation of cell expansion and cartilage regeneration. Methods Mol Biol 1577:147–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li WJ, Jiang YJ, Tuan RS (2006) Chondrocyte phenotype in engineered fibrous matrix is regulated by fiber size. Tissue Eng 12(7):1775–1785

    Article  CAS  PubMed  Google Scholar 

  • Li Z et al (2010) Chondrogenesis of human bone marrow mesenchymal stem cells in fibrin-polyurethane composites is modulated by frequency and amplitude of dynamic compression and shear stress. Tissue Eng Part A 16(2):575–584

    Article  CAS  PubMed  Google Scholar 

  • Liu X et al (2010) In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes. Biomaterials 31(36):9406–9414

    Article  CAS  PubMed  Google Scholar 

  • Liu Q et al (2018) Suppressing mesenchymal stem cell hypertrophy and endochondral ossification in 3D cartilage regeneration with nanofibrous poly(l-lactic acid) scaffold and matrilin-3. Acta Biomater 76:29–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Longhini ALF et al (2019) Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horses. PLoS One 14(3):e0212642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y et al (2006) Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair. J Orthop Res 24(6):1261–1270

    Article  PubMed  Google Scholar 

  • Magri C et al (2019) Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: A clinical pilot study. PLoS One 14(8):e0221317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maki CB et al (2020) Intra-articular administration of allogeneic adipose derived MSCs reduces pain and lameness in dogs with hip osteoarthritis: a double blinded, randomized, placebo controlled pilot study. Front Vet Sci 7:570

    Article  PubMed  PubMed Central  Google Scholar 

  • Mantyh PW et al (2011) Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology 115(1):189–204

    Article  PubMed  Google Scholar 

  • Marinas-Pardo L et al (2018) Allogeneic adipose-derived mesenchymal stem cells (Horse Allo 20) for the treatment of osteoarthritis-associated lameness in horses: characterization, safety, and efficacy of intra-articular treatment. Stem Cells Dev 27(17):1147–1160

    Article  CAS  PubMed  Google Scholar 

  • Martino S et al (2012) Stem cell-biomaterial interactions for regenerative medicine. Biotechnol Adv 30(1):338–351

    Article  CAS  PubMed  Google Scholar 

  • Masri M et al (2007) Matrix-encapsulation cell-seeding technique to prevent cell detachment during arthroscopic implantation of matrix-induced autologous chondrocytes. Arthroscopy 23(8):877–883

    Article  PubMed  Google Scholar 

  • Matsuda H et al (1991) Nerve growth factor-like activity detected in equine peripheral blood after running exercise. Zentralbl Veterinarmed A 38(7):557–559

    Article  CAS  PubMed  Google Scholar 

  • Maumus M et al (2013) Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis. Stem Cell Res 11(2):834–844

    Article  CAS  PubMed  Google Scholar 

  • McCarty EC et al (2016) Fresh osteochondral allograft versus autograft: twelve-month results in isolated canine knee defects. Am J Sports Med 44(9):2354–2365

    Article  PubMed  Google Scholar 

  • McCarthy J et al (2020) Elbow arthrodesis using a medially positioned plate in 6 dogs. Vet Comp Orthop Traumatol 33(1):51–58

    Article  PubMed  Google Scholar 

  • McGonagle D, Baboolal TG, Jones E (2017) Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nat Rev Rheumatol 13(12):719–730

    Article  CAS  PubMed  Google Scholar 

  • Mehana EE, Khafaga AF, El-Blehi SS (2019) The role of matrix metalloproteinases in osteoarthritis pathogenesis: an updated review. Life Sci 234:116786

    Article  CAS  PubMed  Google Scholar 

  • Meirelles Lda S et al (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20(5-6):419–427

    Article  PubMed  Google Scholar 

  • Mello MA, Tuan RS (1999) High density micromass cultures of embryonic limb bud mesenchymal cells: an in vitro model of endochondral skeletal development. In Vitro Cell Dev Biol Anim 35(5):262–269

    Article  CAS  PubMed  Google Scholar 

  • Mensing N et al (2011) Isolation and characterization of multipotent mesenchymal stromal cells from the gingiva and the periodontal ligament of the horse. BMC Vet Res 7:42

    Article  PubMed  PubMed Central  Google Scholar 

  • Meretoja VV et al (2013) The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds. Biomaterials 34(17):4266–4273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Min BH et al (2007) The fate of implanted autologous chondrocytes in regenerated articular cartilage. Proc Inst Mech Eng H 221(5):461–465

    Article  PubMed  Google Scholar 

  • Mirza MH et al (2016) Gait changes vary among horses with naturally occurring osteoarthritis following intra-articular administration of autologous platelet-rich plasma. Front Vet Sci 3:29

    Article  PubMed  PubMed Central  Google Scholar 

  • Mobasheri A et al (2017) The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol 13(5):302–311

    Article  CAS  PubMed  Google Scholar 

  • Mohoric L et al (2016) Blinded placebo study of bilateral osteoarthritis treatment using adipose derived mesenchymal stem cells. Slov Vet Res 53(3):167–174

    Google Scholar 

  • Morrison SJ et al (1997) Identification of a lineage of multipotent hematopoietic progenitors. Development 124(10):1929–1939

    Article  CAS  PubMed  Google Scholar 

  • Mueller MB, Tuan RS (2008) Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells. Arthritis Rheum 58(5):1377–1388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mueller MB et al (2013) Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis. Int Orthop 37(5):945–951

    Article  PubMed  PubMed Central  Google Scholar 

  • Muir P et al (2016) Autologous bone marrow-derived mesenchymal stem cells modulate molecular markers of inflammation in dogs with cruciate ligament rupture. PLoS One 11(8):e0159095

    Article  PubMed  PubMed Central  Google Scholar 

  • Muttigi MS et al (2020) Matrilin-3-primed adipose-derived mesenchymal stromal cell spheroids prevent mesenchymal stromal-cell-derived chondrocyte hypertrophy. Int J Mol Sci 21(23)

    Google Scholar 

  • Mwale F et al (2006) Limitations of using aggrecan and type X collagen as markers of chondrogenesis in mesenchymal stem cell differentiation. J Orthop Res 24(8):1791–1798

    Article  CAS  PubMed  Google Scholar 

  • Mwale F et al (2010) Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients. Tissue Eng Part A 16(11):3449–3455

    Article  CAS  PubMed  Google Scholar 

  • Nakase T et al (2002) Distribution of genes for parathyroid hormone (PTH)-related peptide, Indian hedgehog, PTH receptor and patched in the process of experimental spondylosis in mice. J Neurosurg 97(1 Suppl):82–87

    CAS  PubMed  Google Scholar 

  • Naruse K et al (2004) Spontaneous differentiation of mesenchymal stem cells obtained from fetal rat circulation. Bone 35(4):850–858

    Article  CAS  PubMed  Google Scholar 

  • Ness MG (2016) The Modified Maquet Procedure (MMP) in dogs: technical development and initial clinical experience. J Am Anim Hosp Assoc 52(4):242–250

    Article  PubMed  Google Scholar 

  • Nganvongpanit K et al (2009) Prospective evaluation of serum biomarker levels and cartilage repair by autologous chondrocyte transplantation and subchondral drilling in a canine model. Arthritis Res Ther 11(3):R78

    Article  PubMed  PubMed Central  Google Scholar 

  • Nicpon J, Marycz K, Grzesiak J (2013) Therapeutic effect of adipose-derived mesenchymal stem cell injection in horses suffering from bone spavin. Pol J Vet Sci 16(4):753–754

    Article  CAS  PubMed  Google Scholar 

  • Nishiwaki H et al (2017) A novel method to induce cartilage regeneration with cubic microcartilage. Cells Tissues Organs 204(5-6):251–260

    Article  CAS  PubMed  Google Scholar 

  • Nixon AJ et al (2011) Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full- and partial-thickness cartilage defects in an equine model. J Orthop Res 29(7):1121–1130

    Article  CAS  PubMed  Google Scholar 

  • Nixon AJ et al (2015) A chondrocyte infiltrated collagen type I/III membrane (MACI(R) implant) improves cartilage healing in the equine patellofemoral joint model. Osteoarthr Cartil 23(4):648–660

    Article  CAS  Google Scholar 

  • Nixon AJ et al (2017) Matrix-induced Autologous Chondrocyte Implantation (MACI) using a cell-seeded collagen membrane improves cartilage healing in the equine model. J Bone Joint Surg Am 99(23):1987–1998

    Article  PubMed  Google Scholar 

  • Nürnberger S et al (2006) Ultrastructural insights into the world of cartilage: electron microscopy of articular cartilage. Osteosynth Trauma Care 14(03):168–180

    Article  Google Scholar 

  • Nuernberger S et al (2011) The influence of scaffold architecture on chondrocyte distribution and behavior in matrix-associated chondrocyte transplantation grafts. Biomaterials 32(4):1032–1040

    Article  CAS  PubMed  Google Scholar 

  • Nurnberger S et al (2021) Repopulation of decellularised articular cartilage by laser-based matrix engraving. EBioMedicine 64:103196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Driscoll SW, Fitzsimmons JS (2001) The role of periosteum in cartilage repair. Clin Orthop Relat Res 391:S190–S207

    Article  Google Scholar 

  • O’Conor CJ, Case N, Guilak F (2013) Mechanical regulation of chondrogenesis. Stem Cell Res Ther 4(4):61

    Article  PubMed  PubMed Central  Google Scholar 

  • Olvera D et al (2017) Modulating microfibrillar alignment and growth factor stimulation to regulate mesenchymal stem cell differentiation. Acta Biomater 64:148–160

    Article  CAS  PubMed  Google Scholar 

  • Pacini S et al (2007) Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses. Tissue Eng 13(12):2949–2955

    Article  PubMed  Google Scholar 

  • Patil AS, Sable RB, Kothari RM (2012) Role of insulin-like growth factors (IGFs), their receptors and genetic regulation in the chondrogenesis and growth of the mandibular condylar cartilage. J Cell Physiol 227(5):1796–1804

    Article  CAS  PubMed  Google Scholar 

  • Pei M et al (2009) Histone deacetylase 4 promotes TGF-beta1-induced synovium-derived stem cell chondrogenesis but inhibits chondrogenically differentiated stem cell hypertrophy. Differentiation 78(5):260–268

    Article  CAS  PubMed  Google Scholar 

  • Pelosi M et al (2013) Parathyroid hormone-related protein is induced by hypoxia and promotes expression of the differentiated phenotype of human articular chondrocytes. Clin Sci (Lond) 125(10):461–470

    Article  CAS  Google Scholar 

  • Pelttari K et al (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54(10):3254–3266

    Article  CAS  PubMed  Google Scholar 

  • Prado AA et al (2015) Characterization of mesenchymal stem cells derived from the equine synovial fluid and membrane. BMC Vet Res 11:281

    Article  PubMed  PubMed Central  Google Scholar 

  • Pritzker KP et al (1977) Articular cartilage transplantation. Hum Pathol 8(6):635–651

    Article  CAS  PubMed  Google Scholar 

  • Radtke CL et al (2013) Characterization and osteogenic potential of equine muscle tissue- and periosteal tissue-derived mesenchymal stem cells in comparison with bone marrow- and adipose tissue-derived mesenchymal stem cells. Am J Vet Res 74(5):790–800

    Article  CAS  PubMed  Google Scholar 

  • Raftery RM et al (2016) Multifunctional biomaterials from the sea: Assessing the effects of chitosan incorporation into collagen scaffolds on mechanical and biological functionality. Acta Biomater 43:160–169

    Article  CAS  PubMed  Google Scholar 

  • Rakic R et al (2017) RNA interference and BMP-2 stimulation allows equine chondrocytes redifferentiation in 3D-hypoxia cell culture model: application for matrix-induced autologous chondrocyte implantation. Int J Mol Sci 18(9)

    Google Scholar 

  • Ramezanifard R, Kabiri M, Hanaee Ahvaz H (2017) Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses. EXCLI J 16:1031–1045

    PubMed  PubMed Central  Google Scholar 

  • Ranera B et al (2013) Expansion under hypoxic conditions enhances the chondrogenic potential of equine bone marrow-derived mesenchymal stem cells. Vet J 195(2):248–251

    Article  PubMed  Google Scholar 

  • Ren YJ et al (2009) In vitro behavior of neural stem cells in response to different chemical functional groups. Biomaterials 30(6):1036–1044

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro JCV et al (2017) Versatility of chitosan-based biomaterials and their use as scaffolds for tissue regeneration. Sci World J 2017:8639898

    Article  Google Scholar 

  • Rink BE et al (2017) Isolation and characterization of equine endometrial mesenchymal stromal cells. Stem Cell Res Ther 8(1):166

    Article  PubMed  PubMed Central  Google Scholar 

  • Roach BL et al (2015) Fabrication of tissue engineered osteochondral grafts for restoring the articular surface of diarthrodial joints. Methods 84:103–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rockwood DN et al (2011) Materials fabrication from Bombyx mori silk fibroin. Nat Protoc 6(10):1612–1631

    Article  CAS  PubMed  Google Scholar 

  • Rosadi I et al (2019) In vitro study of cartilage tissue engineering using human adipose-derived stem cells induced by platelet-rich plasma and cultured on silk fibroin scaffold. Stem Cell Res Ther 10(1):369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rucinski K et al (2019) Effects of compliance with procedure-specific postoperative rehabilitation protocols on initial outcomes after osteochondral and meniscal allograft transplantation in the knee. Orthop J Sports Med 7(11):2325967119884291

    Article  PubMed  PubMed Central  Google Scholar 

  • Russlies M et al (2005) Periosteum stimulates subchondral bone densification in autologous chondrocyte transplantation in a sheep model. Cell Tissue Res 319(1):133–142

    Article  PubMed  Google Scholar 

  • Ryan VH et al (2008) NGF gene expression and secretion by canine adipocytes in primary culture: upregulation by the inflammatory mediators LPS and TNFalpha. Horm Metab Res 40(12):861–868

    Article  CAS  PubMed  Google Scholar 

  • Rychel JK (2010) Diagnosis, and treatment of osteoarthritis. Top Companion Anim Med 25(1):20–25

    Article  PubMed  Google Scholar 

  • Salonius E et al (2020) Chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells in a three-dimensional environment. J Cell Physiol 235(4):3497–3507

    Article  CAS  PubMed  Google Scholar 

  • Sanderson RO et al (2009) Systematic review of the management of canine osteoarthritis. Vet Rec 164(14):418–424

    Article  CAS  PubMed  Google Scholar 

  • Sanz-Ramos P et al (2014) Improved chondrogenic capacity of collagen hydrogel-expanded chondrocytes: in vitro and in vivo analyses. J Bone Joint Surg Am 96(13):1109–1117

    Article  PubMed  Google Scholar 

  • Sartore L et al (2021) Polysaccharides on gelatin-based hydrogels differently affect chondrogenic differentiation of human mesenchymal stromal cells. Mater Sci Eng C Mater Biol Appl 126:112175

    Article  CAS  PubMed  Google Scholar 

  • Sasaki A et al (2018) Canine mesenchymal stem cells from synovium have a higher chondrogenic potential than those from infrapatellar fat pad, adipose tissue, and bone marrow. PLoS One 13(8):e0202922

    Article  PubMed  PubMed Central  Google Scholar 

  • Sato K et al (2016) Isolation and characterisation of peripheral blood-derived feline mesenchymal stem cells. Vet J 216:183–188

    Article  CAS  PubMed  Google Scholar 

  • Schaap-Oziemlak AM et al (2014) Biomaterial–stem cell interactions and their impact on stem cell response. RSC Adv 4(95):53307–53320

    Article  CAS  Google Scholar 

  • Schagemann JC et al (2013) Chondrogenic differentiation of bone marrow-derived mesenchymal stromal cells via biomimetic and bioactive poly-epsilon-caprolactone scaffolds. J Biomed Mater Res A 101(6):1620–1628

    Article  CAS  PubMed  Google Scholar 

  • Schreiner AJ et al (2020) Unicompartmental bipolar osteochondral and meniscal allograft transplantation is effective for treatment of medial compartment gonarthrosis in a canine model. J Orthop Res

    Google Scholar 

  • Shah K et al (2018) Outcome of allogeneic adult stem cell therapy in dogs suffering from osteoarthritis and other joint defects. Stem Cells Int 2018:7309201

    Article  PubMed  PubMed Central  Google Scholar 

  • Shintani N, Hunziker EB (2011) Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: influence of microenvironment, tissue origin and growth factor. Eur Cell Mater 22:302–319. discussion 319-20

    Article  CAS  PubMed  Google Scholar 

  • Shortkroff S et al (1996) Healing of chondral and osteochondral defects in a canine model: the role of cultured chondrocytes in regeneration of articular cartilage. Biomaterials 17(2):147–154

    Article  CAS  PubMed  Google Scholar 

  • Slocum B, Slocum TD (1993) Tibial plateau leveling osteotomy for repair of cranial cruciate ligament rupture in the canine. Vet Clin North Am Small Anim Pract 23(4):777–795

    Article  CAS  PubMed  Google Scholar 

  • Smith RK et al (2013) Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy. PLoS One 8(9):e75697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spaas JH et al (2015) Chondrogenic priming at reduced cell density enhances cartilage adhesion of equine allogeneic MSCs – a loading sensitive phenomenon in an organ culture study with 180 explants. Cell Physiol Biochem 37(2):651–665

    Article  CAS  PubMed  Google Scholar 

  • Stefansson SE et al (2003) Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3. Am J Hum Genet 72(6):1448–1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinert AF et al (2012) Indian hedgehog gene transfer is a chondrogenic inducer of human mesenchymal stem cells. Arthritis Res Ther 14(4):R168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevenson S et al (1989) The fate of articular cartilage after transplantation of fresh and cryopreserved tissue-antigen-matched and mismatched osteochondral allografts in dogs. J Bone Joint Surg Am 71(9):1297–1307

    Article  CAS  PubMed  Google Scholar 

  • Stevenson S, Shaffer JW, Goldberg VM (1996) The humoral response to vascular and nonvascular allografts of bone. Clin Orthop Relat Res 326:86–95

    Article  Google Scholar 

  • Stockwell RA (1971) The interrelationship of cell density and cartilage thickness in mammalian articular cartilage. J Anat 109(Pt 3):411–421

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stockwell RA (1978) Chondrocytes. J Clin Pathol Suppl (R Coll Pathol) 12:7–13

    Article  CAS  Google Scholar 

  • Stoker AM et al (2018) Bone marrow aspirate concentrate versus platelet rich plasma to enhance osseous integration potential for osteochondral allografts. J Knee Surg 31(4):314–320

    Article  PubMed  Google Scholar 

  • Stupina TA, Stepanov MA, Teplen’kii MP (2015) Role of subchondral bone in the restoration of articular cartilage. Bull Exp Biol Med 158(6):820–823

    Article  CAS  PubMed  Google Scholar 

  • Stupina TA, Makushin VD, Stepanov MA (2012) Experimental morphological study of the effects of subchondral tunnelization and bone marrow stimulation on articular cartilage regeneration. Bull Exp Biol Med 153(2):289–293

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Tan H (2013) Alginate-based biomaterials for regenerative medicine applications. Materials (Basel) 6(4):1285–1309

    Article  CAS  Google Scholar 

  • Tamada Y, Ikada Y (1993) Effect of preadsorbed proteins on cell adhesion to polymer surfaces. J Colloid Interface Sci 155(2):334–339

    Article  CAS  Google Scholar 

  • Tchetina EV, Squires G, Poole AR (2005) Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. J Rheumatol 32(5):876–886

    CAS  PubMed  Google Scholar 

  • Thorpe SD et al (2012) European Society of Biomechanics S.M. Perren Award 2012: the external mechanical environment can override the influence of local substrate in determining stem cell fate. J Biomech 45(15):2483–2492

    Article  PubMed  Google Scholar 

  • Tibbitt MW, Anseth KS (2009) Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103(4):655–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toh WS et al (2012) Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid hydrogel microenvironment. Biomaterials 33(15):3835–3845

    Article  CAS  PubMed  Google Scholar 

  • Tomlinson RE et al (2017) NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice. Proc Natl Acad Sci U S A 114(18):E3632–E3641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueno T et al (2001) Cellular origin of endochondral ossification from grafted periosteum. Anat Rec 264(4):348–357

    Article  CAS  PubMed  Google Scholar 

  • Vainieri ML et al (2020) Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation. Acta Biomater 101:293–303

    Article  CAS  PubMed  Google Scholar 

  • Veilleux NH, Yannas IV, Spector M (2004) Effect of passage number and collagen type on the proliferative, biosynthetic, and contractile activity of adult canine articular chondrocytes in type I and II collagen-glycosaminoglycan matrices in vitro. Tissue Eng 10(1-2):119–127

    Article  CAS  PubMed  Google Scholar 

  • Venator KP et al (2020) Assessment of a single intra-articular stifle injection of pure platelet rich plasma on symmetry indices in dogs with unilateral or bilateral stifle osteoarthritis from long-term medically managed cranial cruciate ligament disease. Vet Med (Auckl) 11:31–38

    Google Scholar 

  • Vilar JM et al (2013) Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Vet Res 9:131

    Article  PubMed  PubMed Central  Google Scholar 

  • Vilar JM et al (2018) Effect of leukocyte-reduced platelet-rich plasma on osteoarthritis caused by cranial cruciate ligament rupture: a canine gait analysis model. PLoS One 13(3):e0194752

    Article  PubMed  PubMed Central  Google Scholar 

  • Voga M et al (2020) Stem cells in veterinary medicine-current state and treatment options. Front Vet Sci 7:278

    Article  PubMed  PubMed Central  Google Scholar 

  • Walker GD et al (1995) Expression of type-X collagen in osteoarthritis. J Orthop Res 13(1):4–12

    Article  CAS  PubMed  Google Scholar 

  • Webb TL, Quimby JM, Dow SW (2012) In vitro comparison of feline bone marrow-derived and adipose tissue-derived mesenchymal stem cells. J Feline Med Surg 14(2):165–168

    Article  PubMed  Google Scholar 

  • Webster RP, Anderson GI, Gearing DP (2014) Canine brief pain inventory scores for dogs with osteoarthritis before and after administration of a monoclonal antibody against nerve growth factor. Am J Vet Res 75(6):532–535

    Article  CAS  PubMed  Google Scholar 

  • Weiss S et al (2010) Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J Cell Physiol 223(1):84–93

    CAS  PubMed  Google Scholar 

  • Xu X et al (2013) Cultivation and spontaneous differentiation of rat bone marrow-derived mesenchymal stem cells on polymeric surfaces. Clin Hemorheol Microcirc 55(1):143–156

    Article  PubMed  Google Scholar 

  • Yang C et al (2009) The differential in vitro and in vivo responses of bone marrow stromal cells on novel porous gelatin-alginate scaffolds. J Tissue Eng Regen Med 3(8):601–614

    Article  CAS  PubMed  Google Scholar 

  • Yang Q et al (2008) A cartilage ECM-derived 3-D porous acellular matrix scaffold for in vivo cartilage tissue engineering with PKH26-labeled chondrogenic bone marrow-derived mesenchymal stem cells. Biomaterials 29(15):2378–2387

    Article  CAS  PubMed  Google Scholar 

  • Yang X et al (2014) Matrilin-3 inhibits chondrocyte hypertrophy as a bone morphogenetic protein-2 antagonist. J Biol Chem 289(50):34768–34779

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang Z et al (2021) 3D-bioprinted difunctional scaffold for in situ cartilage regeneration based on aptamer-directed cell recruitment and growth factor-enhanced cell chondrogenesis. ACS Appl Mater Interfaces 13(20):23369–23383

    Article  CAS  PubMed  Google Scholar 

  • Yoo JU et al (1998) The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells. J Bone Joint Surg Am 80(12):1745–1757

    Article  CAS  PubMed  Google Scholar 

  • Zamanlui S et al (2018) Enhanced chondrogenic differentiation of human bone marrow mesenchymal stem cells on PCL/PLGA electrospun with different alignments and compositions. Int J Polym Mater Polym Biomater 67(1):50–60

    Article  CAS  Google Scholar 

  • Zhang L et al (2010) Chondrogenic differentiation of human mesenchymal stem cells: a comparison between micromass and pellet culture systems. Biotechnol Lett 32(9):1339–1346

    Article  CAS  PubMed  Google Scholar 

  • Zhang T et al (2015) Cross-talk between TGF-beta/SMAD and integrin signaling pathways in regulating hypertrophy of mesenchymal stem cell chondrogenesis under deferral dynamic compression. Biomaterials 38:72–85

    Article  PubMed  Google Scholar 

  • Zhang BY et al (2018) Evaluation of the curative effect of umbilical cord mesenchymal stem cell therapy for knee arthritis in dogs using imaging technology. Stem Cells Int 2018:1983025

    Article  PubMed  PubMed Central  Google Scholar 

  • Zheng L et al (2021) The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res Rev 66:101249

    Article  CAS  PubMed  Google Scholar 

  • Zhou N et al (2015) HIF-1alpha as a regulator of BMP2-induced chondrogenic differentiation, osteogenic differentiation, and endochondral ossification in stem cells. Cell Physiol Biochem 36(1):44–60

    Article  PubMed  Google Scholar 

  • Zylinska B et al (2018) Treatment of articular cartilage defects: focus on tissue engineering. In Vivo 32(6):1289–1300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Institute for Preclinical Sciences, University of Ljubljana, Ljubljana, Slovenia

    Metka Voga & Gregor Majdic

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  1. Metka Voga
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  2. Gregor Majdic
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Correspondence to Gregor Majdic .

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  1. (emeritus) Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

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Voga, M., Majdic, G. (2022). Articular Cartilage Regeneration in Veterinary Medicine. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 17. Advances in Experimental Medicine and Biology(), vol 1401. Springer, Cham. https://doi.org/10.1007/5584_2022_717

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