Advertisement

Cell and Tissue Research

, Volume 375, Issue 2, pp 329–344 | Cite as

Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis

  • Suleiman Alhaji Muhammad
  • Norshariza Nordin
  • Muhammad Zulfadli Mehat
  • Sharida FakuraziEmail author
Review
  • 191 Downloads

Abstract

Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0–100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials.

Graphical abstract

Keywords

Animal trial Cartilage regeneration Secretome Stem cells Systematic review 

Notes

Acknowledgements

This work was supported by the Universiti Putra Malaysia Research Grant (No. GPIPS/2017/9578600).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

441_2018_2884_MOESM1_ESM.docx (39 kb)
ESM 1 (DOCX 39 kb)
441_2018_2884_MOESM2_ESM.pdf (294 kb)
ESM 2 (PDF 293 kb)
441_2018_2884_MOESM3_ESM.pdf (2.5 mb)
ESM 3 (PDF 2.51 mb)

References

  1. Akpancar S, Tatar O, Turgut H, Akyildiz F, Ekinci S (2016) The current perspectives of stem cell therapy in orthopedic surgery. Arch Trauma Res 5(4):e37976Google Scholar
  2. Al Faqeh H, Nor Hamdan BMY, Chen HC, Aminuddin BS, Ruszymah BHI (2012) The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol 47:458–464Google Scholar
  3. Ando W, Tateishi K, Hart DA, Katakai D, Tanaka Y, Nakata K, Hashimoto J, Fujie H, Shino K, Yoshikawa H, Nakamura N (2007) Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. Biomaterials 28:5462–5470Google Scholar
  4. Angele P, Johnstone B, Kujat R, Zellner J, Nerlich M, Goldberg V, Yoo J (2008) Stem cell based tissue engineering for meniscus repair. J Biomed Mater Res A 85:445–455Google Scholar
  5. Baraniak PR, McDevitt TC (2010) Stem cell paracrine actions and tissue regeneration. Regen Med 5:121–143Google Scholar
  6. Barron V, Merghani K, Shaw G, Coleman CM, Hayes JS, Ansboro S, Manian A, O’Malley G, Connolly E, Nandakumar A, van Blitterswijk CA, Habibovic P, Moroni L, Shannon F, Murphy JM, Barry F (2015) Evaluation of cartilage repair by mesenchymal stem cells seeded on a PEOT/PBT scaffold in an osteochondral defect. Ann Biomed Eng 43:2069–2082Google Scholar
  7. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101Google Scholar
  8. Bentley G, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RWJ (2012) Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. J Bone Joint Surg (Br) 94:504–509Google Scholar
  9. Bhandari M, Smith J, Miller LE, Block JE (2012) Clinical and economic burden of revision knee arthroplasty. Clin Med Insights Arthritis Musculoskelet Disord 5:89–94Google Scholar
  10. Caldwell KL, Wang J (2015) Cell-based articular cartilage repair: the link between development and regeneration. Osteoarthr Cartil 23:351–362Google Scholar
  11. Caminal M, Moll X, Codina D, Rabanal RM, Morist A, Barrachina J, Garcia F, Pla A, Vives J (2014) Transitory improvement of articular cartilage characteristics after implantation of polylactide:polyglycolic acid (PLGA) scaffolds seeded with autologous mesenchymal stromal cells in a sheep model of critical-sized chondral defect. Biotechnol Lett 38:2143–2153Google Scholar
  12. Caminal M, Peris D, Fonseca C, Barrachina J, Codina D, Rabanal RM, Moll X, Morist A, García F, Cairó JJ, Gòdia F, Pla A, Vives J (2016) Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage, fat, and bone marrow in an ovine model of osteochondral focal defect. Cytotechnology 68:907–919Google Scholar
  13. Ceylan HH, Bilsel K, Buyukpinarbasili N, Ceylan H, Erdil M, Tuncay I, Sen C (2016) Can chondral healing be improved following microfracture? The effect of adipocyte tissue derived stem cell therapy. Knee 23:442–449Google Scholar
  14. Chang CH, Kuo TF, Lin FH, Wang JH, Hsu YM, Huang HT, Loo ST, Fang HW, Liu HC, Wang WC (2011) Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model. J Orthop Res 29:1874–1880Google Scholar
  15. Chang F, Ishii T, Yanai T, Mishima H, Akaogi H, Ogawa T, Ochiai N (2008) Repair of large full-thickness articular cartilage defects by transplantation of autologous uncultured bone-marrow-derived mononuclear cells. J Orthop Res 26:18–26Google Scholar
  16. Chiang ER, Ma HL, Wang JP, Liu CL, Chen TH, Hung SC (2016) Allogeneic mesenchymal stem cells in combination with hyaluronic acid for the treatment of osteoarthritis in rabbits. PLoS One 11:e0149835Google Scholar
  17. Chijimatsu R, Ikeya M, Yasui Y, Ikeda Y, Ebina K, Moriguchi Y, Shimomura K, Hart DA, Hideki Y, Norimasa N (2017) Characterization of mesenchymal stem cell-like cells derived from human iPSCs via neural crest development and their application for osteochondral repair. Stem Cells Int 2017:1960965Google Scholar
  18. Chung JY, Song M, Ha CW, Kim JA, Lee CH, Park YB (2014) Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res Ther 5:39.  https://doi.org/10.1186/scrt427 Google Scholar
  19. Dai L, He Z, Zhang X, Hu X, Yuan L, Qiang M, Zhu J, Shao Z, Zhou C, Ao Y (2014) One-step repair for cartilage defects in a rabbit model: a technique combining the perforated decalcified cortical-cancellous bone matrix scaffold with microfracture. Am J Sports Med 42:583–591Google Scholar
  20. Dai NT, Fan GY, Liou NH, Wang YW, Fu KY, Ma KH, Liu JC, Chang SC, Huang KL, Dai LG, Chen SG, Chen TM, Chen TM (2015) Histochemical and functional improvement of adipose-derived stem cell-based tissue-engineered cartilage by hyperbaric oxygen/air treatment in a rabbit articular defect model. Ann Plast Surg 74(Suppl 2):S139–S145Google Scholar
  21. Dashtdar H, Murali MR, Abbas AA, Suhaeb AM, Selvaratnam L, Tay LX, Kamarul T (2015) PVA-chitosan composite hydrogel versus alginate beads as a potential mesenchymal stem cell carrier for the treatment of focal cartilage defects. Knee Surg Sports Traumatol Arthrosc 23:1368–1377Google Scholar
  22. Dashtdar H, Rothan HA, Tay T, Ahmad RE, Ali R, Tay LX, Chong PP, Kamarul T (2011) A preliminary study comparing the use of allogenic chondrogenic pre-differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits. J Orthop Res 29:1336–1342Google Scholar
  23. Dattena M, Pilichi S, Rocca S, Mara L, Casu S, Masala G, Manunta A, Passino ES, Pool RR, Cappai P (2009) Sheep embryonic stem-like cells transplanted in full-thickness cartilage defects. J Tissue Eng Regen Med 3:175–187Google Scholar
  24. Davatchi F, Sadeghi Abdollahi B, Mohyeddin M, Nikbin B (2016) Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis 19:219–225Google Scholar
  25. Delling U, Brehm W, Ludewig E, Winter K, Jülke H (2015) Longitudinal evaluation of effects of intra-articular mesenchymal stromal cell administration for the treatment of osteoarthritis in an ovine model. Cell Transplant 24:2391–2407Google Scholar
  26. Deng J, She R, Huang W, Dong Z, Mo G, Liu B (2013) A silk fibroin/chitosan scaffold in combination with bone marrow-derived mesenchymal stem cells to repair cartilage defects in the rabbit knee. J Mater Sci Mater Med 24:2037–2046Google Scholar
  27. Duan P, Pan Z, Cao L, He Y, Wang H, Qu Z, Dong J, Ding J (2014) The effects of pore size in bilayered poly(lactide-co-glycolide) scaffolds on restoring osteochondral defects in rabbits. J Biomed Mater Res A 102:180–192Google Scholar
  28. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634Google Scholar
  29. Fekrazad R, Eslaminejad MB, Shayan AM, Kalhori KAM, Abbas FM, Taghiyar L, Sepehr Pedram M, Ghuchani M (2016) Effects of photobiomodulation and mesenchymal stem cells on articular cartilage defects in a rabbit model. Photomed Laser Surg 34:543–549Google Scholar
  30. Fisher MB, Belkin NS, Milby AH, Henning EA, Söegaard N, Kim M, Pfeifer C, Saxena V, Dodge GR, Burdick JA, Schaer TP, Steinberg DR, Mauck RL (2016) Effects of mesenchymal stem cell and growth factor delivery on cartilage repair in a mini-pig model. Cartilage 7:174–184Google Scholar
  31. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A (2016) Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy—a review. BMC Musculoskelet Disord 17:230Google Scholar
  32. Fu WL, Zhou CY, Yu JK (2014) A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model. Am J Sports Med 42:592–601Google Scholar
  33. Goldberg A, Mitchell K, Soans J, Kim L, Zaidi R (2017) The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review. J Orthop Surg 12:39Google Scholar
  34. Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR (2016) Addition of mesenchymal stem cells to autologous platelet-enhanced fibrin scaffolds in chondral defects: does it enhance repair? J Bone Joint Surg Am 98:23–34Google Scholar
  35. Guillén-García P, Rodríguez-Iñigo E, Guillén-Vicente I, Caballero-Santos R, Guillén-Vicente M, Abelow S, Giménez-Gallego G, López-Alcorocho JM (2014) Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage 5:114–122Google Scholar
  36. Ha CW, Park YB, Chung JY, Park YG (2015) Cartilage repair using composites of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel in a minipig model. Stem Cells Transl Med 4:1044–1051Google Scholar
  37. Hatsushika D, Muneta T, Horie M, Koga H, Tsuji K, Sekiya I (2013) Intraarticular injection of synovial stem cells promotes meniscal regeneration in a rabbit massive meniscal defect model. J Orthop Res 31:1354–1359Google Scholar
  38. Hatsushika D, Muneta T, Nakamura T, Horie M, Koga H, Nakagawa Y, Tsuji K, Hishikawa S, Kobayashi E, Sekiya I (2014) Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model. Osteoarthr Cartil 22:941–950Google Scholar
  39. Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J, Van Dijk CN (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20:423–435Google Scholar
  40. Henderson VC, Kimmelman J, Fergusson D, Grimshaw JM, Hackam DG (2013) Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments. PLoS Med 10:e1001489Google Scholar
  41. Hermeto LC, DeRossi R, Oliveira RJ, Pesarini JR, Antoniolli-Silva AC, Jardim PH, Santana AE, Deffune E, Rinaldi JC, Justulin LA (2016) Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis. Genet Mol Res 15(3).  https://doi.org/10.4238/gmr.15038569
  42. Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14:43Google Scholar
  43. Hopper N, Wardale J, Brooks R, Power J, Rushton N, Henson F (2015) Peripheral blood mononuclear cells enhance cartilage repair in in vivo osteochondral defect model. PLoS One 10:e0133937Google Scholar
  44. Horie M, Choi H, Lee RH, Reger RL, Ylostalo J, Muneta T, Sekiya I, Prockop DJ (2012a) Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthr Cartil 20:1197–1207Google Scholar
  45. Horie M, Driscoll MD, Sampson HW, Sekiya I, Caroom CT, Prockop DJ, Thomas DB (2012b) Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model. J Bone Joint Surg Am 94:701–712Google Scholar
  46. Hu B, Ren JL, Zhang JR, Ma Q, Liu YP, Mao TQ (2010) Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit model. J Tissue Eng Regen Med 4:105–114Google Scholar
  47. Hui JHP, Chen F, Thambyah A, Lee EH (2004) Treatment of chondral lesions in advanced osteochondritis dissecans: a comparative study of the efficacy of chondrocytes, mesenchymal stem cells, periosteal graft, and mosaicplasty (osteochondral autograft) in animal models. J Pediatr Orthop 24:427–433Google Scholar
  48. Hui TY, Cheung KMC, Cheung WL, Chan D, Chan BP (2008) In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration. Biomaterials 29:3201–3212Google Scholar
  49. Itokazu M, Wakitani S, Mera H, Tamamura Y, Sato Y, Takagi M, Nakamura H (2016) Transplantation of scaffold-free cartilage-like cell-sheets made from human bone marrow mesenchymal stem cells for cartilage repair: a preclinical study. Cartilage 7:361–372Google Scholar
  50. Jang KM, Lee JH, Park CM, Song HR, Wang JH (2014) Xenotransplantation of human mesenchymal stem cells for repair of osteochondral defects in rabbits using osteochondral biphasic composite constructs. Knee Surg Sports Traumatol Arthrosc 22:1434–1444Google Scholar
  51. Javanmard MZ, Asgari D, Karimipour M, Atabaki F, Farjah G, Niakani A (2015) Mesenchymal stem cells inhibit proteoglycan degeneration in a rat model of osteoarthritis. Gene Cell Tissue 2(4):e31011Google Scholar
  52. Jia S, Zhang T, Xiong Z, Pan W, Liu J, Sun W (2015) In vivo evaluation of a novel oriented scaffold-BMSC construct for enhancing full-thickness articular cartilage repair in a rabbit model. PLoS One 10:e0145667Google Scholar
  53. Jiang L, Ma A, Song L, Hu Y, Dun H, Daloze P, Yu Y, Jiang J, Zafarullah M, Chen H (2014) Cartilage regeneration by selected chondrogenic clonal mesenchymal stem cells in the collagenase-induced monkey osteoarthritis model. J Tissue Eng Regen Med 8:896–905Google Scholar
  54. Jing X, Yang L, Duan X, Xie B, Chen W, Li Z, Tan H (2008) In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Jt Bone Spine Rev Rhum 75:432–438Google Scholar
  55. Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32:1254–1266Google Scholar
  56. Jung M, Kaszap B, Redöhl A, Steck E, Breusch S, Richter W, Gotterbarm T (2009) Enhanced early tissue regeneration after matrix-assisted autologous mesenchymal stem cell transplantation in full thickness chondral defects in a minipig model. Cell Transplant 18:923–932Google Scholar
  57. Kim JE, Lee SM, Kim SH, Tatman P, Gee AO, Kim DH, Lee KE, Jung Y, Kim SJ (2014) Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model. Int J Nanomedicine 9(Suppl 1):141–157Google Scholar
  58. Ko JY, Kim KI, Park S, Im GI (2014) In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 35:3571–3581Google Scholar
  59. Ko JY, Lee J, Lee J, Im GI (2017) Intra-articular xenotransplantation of adipose-derived stromal cells to treat osteoarthritis in a goat model. Tissue Eng Regen Med 14:65–71.  https://doi.org/10.1007/s13770-016-0010-5 Google Scholar
  60. Koga H, Muneta T, Ju YJ, Nagase T, Nimura A, Mochizuki T, Ichinose S, von der Mark, Sekiya I (2007) Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells 25:689–696Google Scholar
  61. Koga H, Shimaya M, Muneta T, Nimura A, Morito T, Hayashi M, Suzuki S, Ju YJ, Mochizuki T, Sekiya I (2008) Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther 10:R84.  https://doi.org/10.1186/ar2460 Google Scholar
  62. Kreuz PC, Müller S, Ossendorf C, Kaps C, Erggelet C (2009) Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther 11:R33Google Scholar
  63. Lam J, Lu S, Lee EJ, Trachtenberg JE, Meretoja VV, Dahlin RL, van den Beucken JJ, Tabata Y, Wong ME, Jansen JA, Mikos AG, Kasper FK (2014) Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model. Osteoarthr Cartil 22:1291–1300Google Scholar
  64. Latief N, Raza FA, Bhatti FUR, Tarar MN, Khan SN, Riazuddin S (2016) Adipose stem cells differentiated chondrocytes regenerate damaged cartilage in rat model of osteoarthritis. Cell Biol Int 40:579–588Google Scholar
  65. Lee JC, Lee SY, Min HJ, Han SA, Jang J, Lee S, Seong SC, Lee MC (2012) Synovium-derived mesenchymal stem cells encapsulated in a novel injectable gel can repair osteochondral defects in a rabbit model. Tissue Eng A 18:2173–2186Google Scholar
  66. Lee JC, Min HJ, Park HJ, Lee S, Seong SC, Lee MC (2013) Synovial membrane–derived mesenchymal stem cells supported by platelet-rich plasma can repair osteochondral defects in a rabbit model. Arthroscopy 29:1034–1046Google Scholar
  67. Lee KBL, Hui JHP, Song IC, Ardany L, Lee EH (2007) Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model. Stem Cells 25:2964–2971Google Scholar
  68. Leonard CA, Lee W-Y, Tailor P, Salo PT, Kubes P, Krawetz RJ (2015) Allogeneic bone marrow transplant from MRL/MpJ super-healer mice does not improve articular cartilage repair in the C57Bl/6 strain. PLoS One 10:e0131661Google Scholar
  69. Li WJ, Chiang H, Kuo TF, Lee HS, Jiang CC, Tuan RS (2009) Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study. J Tissue Eng Regen Med 3:1–10Google Scholar
  70. Lin Z, Fitzgerald JB, Xu J, Willers C, Wood D, Grodzinsky AJ, Zheng MH (2008) Gene expression profiles of human chondrocytes during passaged monolayer cultivation. J Orthop Res 26:1230–1237Google Scholar
  71. Liu S, Jia Y, Yuan M, Guo W, Huang J, Zhao B, Peng J, Xu W, Lu S, Guo Q (2017) Repair of osteochondral defects using human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in a rabbit model. Biomed Res Int 2017:8760383Google Scholar
  72. Løken S, Jakobsen RB, Arøen A, Heir S, Shahdadfar A, Brinchmann JE, Engebretsen L, Reinholt FP (2008) Bone marrow mesenchymal stem cells in a hyaluronan scaffold for treatment of an osteochondral defect in a rabbit model. Knee Surg Sports Traumatol Arthrosc 16:896–903Google Scholar
  73. Madrigal M, Rao KS, Riordan NH (2014) A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med 12:260Google Scholar
  74. Mahmoud EE, Kamei G, Harada Y, Shimizu R, Kamei N, Adachi N, Misk NA, Ochi M (2016) Cell magnetic targeting system for repair of severe chronic osteochondral defect in a rabbit model. Cell Transplant 25:1073–1083Google Scholar
  75. Mak J, Jablonski CL, Leonard CA, Dunn JF, Raharjo E, Matyas JR, Biernaskie J, Krawetz RJ (2016) Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci Rep 6:23076Google Scholar
  76. Masuoka K, Asazuma T, Hattori H, Yoshihara Y, Sato M, Matsumura K, Matsui T, Takase B, Nemoto K, Ishihara M (2006) Tissue engineering of articular cartilage with autologous cultured adipose tissue-derived stromal cells using atelocollagen honeycomb-shaped scaffold with a membrane sealing in rabbits. J Biomed Mater Res B Appl Biomater 79:25–34Google Scholar
  77. Mata M, Milian L, Oliver M, Zurriaga J, Sancho-Tello M, de Llano JJM, Carda C (2017) In vivo articular cartilage regeneration using human dental pulp stem cells cultured in an alginate scaffold: a preliminary study. Stem Cells Int 2017:8309256Google Scholar
  78. Matsumoto T, Cooper GM, Gharaibeh B, Meszaros LB, Li G, Usas A, Fu FH, Huard J (2009) Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum 60:1390–1405Google Scholar
  79. Maumus M, Roussignol G, Toupet K, Penarier G, Bentz I, Teixeira S, Oustric D, Jung M, Lepage O, Steinberg R, Jorgensen C, Noel D (2016) Utility of a mouse model of osteoarthritis to demonstrate cartilage protection by IFNγ-primed equine mesenchymal stem cells. Front Immunol 7:392Google Scholar
  80. McCarty RC, Xian CJ, Gronthos S, Zannettino AC, Foster BK (2010) Application of autologous bone marrow derived mesenchymal stem cells to an ovine model of growth plate cartilage injury. Open Orthop J 4:204–210Google Scholar
  81. McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM, Kawcak CE, Steadman JR (2011) Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects. Arthroscopy 27:1552–1561Google Scholar
  82. Mehrabani D, Babazadeh M, Tanideh N, Zare S, Hoseinzadeh S, Torabinejad S, Koohi-Hosseinabadi O (2015) The healing effect of adipose-derived mesenchymal stem cells in full-thickness femoral articular cartilage defects of rabbit. Int J Organ Transplant Med 6:165–175Google Scholar
  83. Mei L, Shen B, Ling P, Liu S, Xue J, Liu F, Shao H, Chen J, Ma A, Liu X (2017) Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model. PLoS One 12:e0176107Google Scholar
  84. Meirelles L d S, Fontes AM, Covas DT, Caplan AI (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20:419–427Google Scholar
  85. Mifune Y, Matsumoto T, Murasawa S, Kawamoto A, Kuroda R, Shoji T, Kuroda T, Fukui T, Kawakami Y, Kurosaka M, Asahara T (2013) Therapeutic superiority for cartilage repair by CD271-positive marrow stromal cell transplantation. Cell Transplant 22:1201–1211Google Scholar
  86. Miller RE, Grodzinsky AJ, Vanderploeg EJ, Lee C, Ferris DJ, Barrett MF, Kisiday JD, Frisbie DD (2010) Effect of self-assembling peptide, chondrogenic factors, and bone marrow derived stromal cells on osteochondral repair. Osteoarthr Cartil 18:1608–1619Google Scholar
  87. Mobasheri A, Csaki C, Clutterbuck AL, Rahmanzadeh M, Shakibaei M (2009) Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy. Histol Histopathol 24:347–366Google Scholar
  88. Moher D, Liberati A, Tetzlaff J, Altman DG, Group TP (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097Google Scholar
  89. Mokbel A, El-Tookhy O, Shamaa AA, Sabry D, Rashed L, Mostafa A (2011a) Homing and efficacy of intra-articular injection of autologous mesenchymal stem cells in experimental chondral defects in dogs. Clin Exp Rheumatol 29:275–284Google Scholar
  90. Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM (2011b) Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 12:259Google Scholar
  91. Moran CJ, Ramesh A, Brama PAJ, O’Byrne JM, O’Byrne FJ, Levingstone TJ (2016) The benefits and limitations of animal models for translational research in cartilage repair. J Exp Orthop 3:1Google Scholar
  92. Mrugala D, Bony C, Neves N, Caillot L, Fabre S, Moukoko D, Jorgensen C, Noël D (2008) Phenotypic and functional characterisation of ovine mesenchymal stem cells: application to a cartilage defect model. Ann Rheum Dis 67:288–295Google Scholar
  93. Muhammad SA, Nordin N, Fakurazi S (2018) Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies. Rev Neurosci 29:321–332Google Scholar
  94. Murdoch AD, Grady LM, Ablett MP, Katopodi T, Meadows RS, Hardingham TE (2007) Chondrogenic differentiation of human bone marrow stem cells in transwell cultures: generation of scaffold-free cartilage. Stem Cells 25:2786–2796Google Scholar
  95. Murphy JM, Fink DJ, Hunziker EB, Barry FP (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48:3464–3474Google Scholar
  96. Nakagawa Y, Muneta T, Kondo S, Mizuno M, Takakuda K, Ichinose S, Tabuchi T, Koga H, Tsuji K, Sekiya I (2015) Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs. Osteoarthr Cartil 23:1007–1017Google Scholar
  97. Nakagawa Y, Muneta T, Otabe K, Ozeki N, Mizuno M, Udo M, Saito R, Yanagisawa K, Ichinose S, Koga H, Tsuji K, Sekiya I (2016) Cartilage derived from bone marrow mesenchymal stem cells expresses lubricin in vitro and in vivo. PLoS One 11(2):e0148777Google Scholar
  98. Nakamura T, Sekiya I, Muneta T, Hatsushika D, Horie M, Tsuji K, Kawarasaki T, Watanabe A, Hishikawa S, Fujimoto Y, Tanaka H, Kobayashi E (2012) Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs. Cytotherapy 14:327–338Google Scholar
  99. Nam HY, Karunanithi P, Loo WC, Naveen S, Chen H, Hussin P, Chan L, Kamarul T (2013) The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model. Arthritis Res Ther 15:R129Google Scholar
  100. Necas A, Plánka L, Srnec R, Crha M, Hlucilová J, Klíma J, Starý D, Kren L, Amler E, Vojtová L, Jancár J, Gál P (2010) Quality of newly formed cartilaginous tissue in defects of articular surface after transplantation of mesenchymal stem cells in a composite scaffold based on collagen I with chitosan micro- and nanofibres. Physiol Res 59:605–614Google Scholar
  101. Nejadnik H, Lenkov O, Gassert F, Fretwell D, Lam I, Daldrup-Link HE (2016) Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects. Sci Rep 6:25897Google Scholar
  102. Nishimori M, Deie M, Kanaya A, Exham H, Adachi N, Ochi M (2006) Repair of chronic osteochondral defects in the rat. A bone marrow-stimulating procedure enhanced by cultured allogenic bone marrow mesenchymal stromal cells. J Bone Joint Surg (Br) 88:1236–1244Google Scholar
  103. Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T (2004) Fate of transplanted bone-marrow-derived mesenchymal cells during osteochondral repair using transgenic rats to simulate autologous transplantation. Osteoarthr Cartil 12:811–817Google Scholar
  104. Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T (2005) Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation. J Histochem Cytochem 53:207–216Google Scholar
  105. Ozeki N, Muneta T, Matsuta S, Koga H, Nakagawa Y, Mizuno M, Tsuji K, Mabuchi Y, Akazawa C, Kobayashi E, Matsumoto K, Futamura K, Saito T, Sekiya I (2015) Synovial mesenchymal stem cells promote meniscus regeneration augmented by an autologous Achilles tendon graft in a rat partial meniscus defect model. Stem Cells 33:1927–1938Google Scholar
  106. Panagiotou N, Wayne Davies R, Selman C, Shiels PG (2016) Microvesicles as vehicles for tissue regeneration: changing of the guards. Curr Pathobiol Rep 4:181–187Google Scholar
  107. Park JS, Woo DG, Yang HN, Lim HJ, Park KM, Na K, Park KH (2010) Chondrogenesis of human mesenchymal stem cells encapsulated in a hydrogel construct: neocartilage formation in animal models as both mice and rabbits. J Biomed Mater Res A 92:988–996Google Scholar
  108. Park YB, Ha CW, Kim JA, Han WJ, Rhim JH, Lee HJ, Kim KJ, Park YG, Chung JY (2017) Single-stage cell-based cartilage repair in a rabbit model: cell tracking and in vivo chondrogenesis of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel composite. Osteoarthr Cartil 25:570–580Google Scholar
  109. Park YB, Ha CW, Kim JA, Rhim JH, Park YG, Chung JY, Lee HJ (2016) Effect of transplanting various concentrations of a composite of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel on articular cartilage repair in a rabbit model. PLoS One 11:e0165446Google Scholar
  110. Park YB, Song M, Lee CH, Kim JA, Ha CW (2015) Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model. J Orthop Res 33:1580–1586Google Scholar
  111. Parrilli A, Giavaresi G, Ferrari A, Salamanna F, Desando G, Grigolo B, Martini L, Fini M (2017) Subchondral bone response to injected adipose-derived stromal cells for treating osteoarthritis using an experimental rabbit model. Biotech Histochem 92:201–211Google Scholar
  112. Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH (2017) Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med 51:1125–1133Google Scholar
  113. Pei M, He F, Li J, Tidwell JE, Jones AC, McDonough EB (2013) Repair of large animal partial-thickness cartilage defects through intraarticular injection of matrix-rejuvenated synovium-derived stem cells. Tissue Eng A 19:1144–1154Google Scholar
  114. Pescador D, Ibáñez-Fonseca A, Sánchez-Guijo F, Briñón JG, Arias FJ, Muntión S, Hernández C, Girotti A, Alonso M, Del Cañizo MC, Rodríguez-Cabello JC, Blanco JF (2017) Regeneration of hyaline cartilage promoted by xenogeneic mesenchymal stromal cells embedded within elastin-like recombinamer-based bioactive hydrogels. J Mater Sci Mater Med 28:115Google Scholar
  115. Petchdee S, Suphamungm W, Bootcha R (2016) Therapeutic benefit of intra-articular administration of deciduous teeth stem cells in rabbit model of osteoarthritis. Asian J Anim Vet Adv 11:363–370Google Scholar
  116. Pilichi S, Rocca S, Pool RR, Dattena M, Masala G, Mara L, Sanna D, Casu S, Manunta ML, Manunta A, Passino ES (2014) Treatment with embryonic stem-like cells into osteochondral defects in sheep femoral condyles. BMC Vet Res 10:301Google Scholar
  117. Platas J, Guillén MI, del Caz MDP, Gomar F, Mirabet V, Alcaraz MJ (2013) Conditioned media from adipose-tissue-derived mesenchymal stem cells downregulate degradative mediators induced by interleukin-1β in osteoarthritic chondrocytes. Mediat Inflamm 2013:357014Google Scholar
  118. Pot MW, Gonzales VK, Buma P, IntHout J, van Kuppevelt TH, de Vries RBM, Daamen WF et al (2016) Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies. PeerJ 4:e2243Google Scholar
  119. Proffen BL, Vavken P, Haslauer CM, Fleming BC, Harris CE, Machan JT, Murray MM (2015) Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model. Am J Sports Med 43:320–330.  https://doi.org/10.1177/0363546514559826 Google Scholar
  120. Qi B, Yu A, Zhu S, Zhou M, Wu G (2013) Chitosan/poly(vinyl alcohol) hydrogel combined with Ad-hTGF-β1 transfected mesenchymal stem cells to repair rabbit articular cartilage defects. Exp Biol Med Maywood NJ 238:23–30Google Scholar
  121. Qi Y, Yang Z, Ding Q, Zhao T, Huang Z, Feng G (2016) Targeted transplantation of iron oxide-labeled, adipose-derived mesenchymal stem cells in promoting meniscus regeneration following a rabbit massive meniscal defect. Exp Ther Med 11:458–466Google Scholar
  122. Qi Y, Zhao T, Xu K, Dai T, Yan W (2012) The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep 39:1231–1237Google Scholar
  123. Rai V, Dilisio MF, Dietz NE, Agrawal DK (2017) Recent strategies in cartilage repair: a systemic review of the scaffold development and tissue engineering. J Biomed Mater Res A 105:2343–2354Google Scholar
  124. Ruiz-Ibán MÁ, Díaz-Heredia J, García-Gómez I, Gonzalez-Lizán F, Elías-Martín E, Abraira V (2011) The effect of the addition of adipose-derived mesenchymal stem cells to a meniscal repair in the avascular zone: an experimental study in rabbits. Arthroscopy 27:1688–1696Google Scholar
  125. Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H (2012) Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther 14:R31Google Scholar
  126. Saulnier N, Viguier E, Perrier-Groult E, Chenu C, Pillet E, Roger T, Maddens S, Boulocher C (2015) Intra-articular administration of xenogeneic neonatal mesenchymal stromal cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis. Osteoarthr Cartil 23:122–133Google Scholar
  127. Schelbergen RF, van Dalen S, ter Huurne M, Roth J, Vogl T, Noël D, Jorgensen C, van den Berg WB, van de Loo FA, Blom AB, van Lent PLEM (2014) Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels. Osteoarthr Cartil 22:1158–1166Google Scholar
  128. Shi J, Zhang X, Zhu J, Pi Y, Hu X, Zhou C, Ao Y (2013) Nanoparticle delivery of the bone morphogenetic protein 4 gene to adipose-derived stem cells promotes articular cartilage repair in vitro and in vivo. Arthroscopy 29:2001–2011Google Scholar
  129. Shim G, Lee S, Han J, Kim G, Jin H, Miao W, Yi TG, Cho YK, Song SU, Oh YK (2014) Pharmacokinetics and in vivo fate of intra-articularly transplanted human bone marrow-derived clonal mesenchymal stem cells. Stem Cells Dev 24:1124–1132Google Scholar
  130. Shim J-H, Jang K-M, Hahn SK, Park JY, Jung H, Oh K, Park KM, Yeom J, Park SH, Kim SW, Wang JH, Kim K, Cho DW (2016) Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. Biofabrication 8:014102Google Scholar
  131. Shimomura K, Ando W, Tateishi K, Nansai R, Fujie H, Hart DA, Gobbi A, Kita K, Horibe S, Shino K, Yoshikawa H, Nakamura N (2010) The influence of skeletal maturity on allogenic synovial mesenchymal stem cell-based repair of cartilage in a large animal model. Biomaterials 31:8004–8011Google Scholar
  132. Singh A, Goel SC, Gupta KK, Kumar M, Arun GR, Patil H, Kumaraswamy V, Jha S (2014) The role of stem cells in osteoarthritis: an experimental study in rabbits. Bone Joint Res 3:32–37Google Scholar
  133. Song F, Tang J, Geng R, Hu H, Zhu C, Cui W, Fan W (2014) Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model. Int J Clin Exp Pathol 7:1415–1426Google Scholar
  134. Sridharan B, Laflin AD, Holtz MA, Pacicca DM, Wischmeier NK, Detamore MS (2017) In vivo evaluation of stem cell aggregates on osteochondral regeneration. J Orthop Res 35:1606–1616Google Scholar
  135. Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002Google Scholar
  136. Suhaeb AM, Naveen S, Mansor A, Kamarul T (2012) Hyaluronic acid with or without bone marrow derived-mesenchymal stem cells improves osteoarthritic knee changes in rat model: a preliminary report. Indian J Exp Biol 50:383–390Google Scholar
  137. Sun J, Hou X-K, Li X, Tang TT, Zhang RM, Kuang Y, Shi M (2009) Mosaicplasty associated with gene enhanced tissue engineering for the treatment of acute osteochondral defects in a goat model. Arch Orthop Trauma Surg 129:757–771Google Scholar
  138. Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ (2017) Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 7:180–195Google Scholar
  139. Tay LX, Ahmad RE, Dashtdar H, Tay KW, Masjuddi T, Ab-Rahim S, Chong PP, Selvaratnam L, Kamarul T (2012) Treatment outcomes of alginate-embedded allogenic mesenchymal stem cells versus autologous chondrocytes for the repair of focal articular cartilage defects in a rabbit model. Am J Sports Med 40:83–90Google Scholar
  140. ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, Jeanson J, Noël D, Casteilla L, Jorgensen C, van den Berg W, van Lent PLEM (2012) Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 64:3604–3613Google Scholar
  141. Toghraie F, Razmkhah M, Gholipour MA, Faghih Z, Chenari N, Torabi Nezhad S, Nazhvani Dehghani S, Ghaderi A (2012) Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med 15:495–499Google Scholar
  142. Toghraie FS, Chenari N, Gholipour MA, Faghih Z, Torabinejad S, Dehghani S, Ghaderi A (2011) Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in rabbit. Knee 18:71–75Google Scholar
  143. Toh WS, Lai RC, Hui JHP, Lim SK (2017) MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. Semin Cell Dev Biol 67:56–64Google Scholar
  144. Toratani T, Nakase J, Numata H, Oshima T, Takata Y, Nakayama K, Tsuchiya H (2017) Scaffold-free tissue-engineered allogenic adipose-derived stem cells promote meniscus healing. Arthroscopy 33:346–354Google Scholar
  145. Ude CC, Ng MH, Chen CH, Htwe O, Amaramalar NS, Hassan S, Djordjevic I, Rani RA, Ahmad J, Yahya NM, Saim AB, Idrus RBH (2015) Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment. Osteoarthr Cartil 23:1294–1306Google Scholar
  146. Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, Saim AB, Idrus RBH (2014) Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model. PLoS One 9:e98770Google Scholar
  147. Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells—current trends and future prospective. Biosci Rep 35:1–18Google Scholar
  148. Uto S, Nishizawa S, Takasawa Y, Asawa Y, Fujihara Y, Takato T, Hoshi K (2013) Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model. Biomed Res 34:281–288Google Scholar
  149. van Buul GM, Siebelt M, Leijs MJC, Bos PK, Waarsing JH, Kops N, Weinans H, Verhaar JA, Bernsen MR, van Osch GJVM (2014) Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis. J Orthop Res 32:1167–1174Google Scholar
  150. Van Pham P, Bui KH-T, Ngo DQ, Vu NB, Truong NH, Phan NLC, Le DM, Duong TD, Nguyen TD, Le VT, Phan NK (2013) Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage. Stem Cell Res Ther 4:91Google Scholar
  151. Vishnubhatla I, Corteling R, Stevanato L, Hicks C, Sinden J (2014) The development of stem cell-derived exosomes as a cell-free regenerative medicine. J Circ Biomark 3:2Google Scholar
  152. Wakayama H, Hashimoto N, Matsushita Y, Matsubara K, Yamamoto N, Hasegawa Y, Ueda M, Yamamoto A (2015) Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice. Cytotherapy 17:1119–1129Google Scholar
  153. Wakitani S, Yamamoto T (2002) Response of the donor and recipient cells in mesenchymal cell transplantation to cartilage defect. Microsc Res Tech 58:14–18Google Scholar
  154. Wakitani S, Aoki H, Harada Y, Sonobe M, Morita Y, Mu Y, Tomita N, Nakamura Y, Takeda S, Watanabe TK, Tanigami A (2004) Embryonic stem cells form articular cartilage, not teratomas, in osteochondral defects of rat joints. Cell Transplant 13:331–336Google Scholar
  155. Wang W, He N, Feng C, Liu V, Zhang L, Wang F, He J, Zhu T, Wang S, Qiao W, Li S, Zhou G, Zhang L, Dai C, Cao W (2015) Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage. Int J Mol Sci 16:12076–12091Google Scholar
  156. Wang Y, Yu D, Liu Z, Zhou F, Dai J, Wu B, Zhou J, Heng BC, Zou XH, Ouyang H, Liu H (2017) Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther 8:189Google Scholar
  157. Wang ZJ, An RZ, Zhao JY, Zhang Q, Yang J, Wang JB, Wen GY, Yuan XH, Qi XW, Li SJ, Ye XC (2014) Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits. Genet Mol Res 13:4599–4606Google Scholar
  158. Wehling P, Moser C, Maixner W (2016) How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts. Ther Adv Musculoskelet Dis 8:72–85Google Scholar
  159. Wilke MM, Nydam DV, Nixon AJ (2007) Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. J Orthop Res 25:913–925Google Scholar
  160. Wolfstadt JI, Cole BJ, Ogilvie-Harris DJ, Viswanathan S, Chahal J (2015) Current concepts: the role of mesenchymal stem cells in the management of knee osteoarthritis. Sports Health 7:38–44Google Scholar
  161. Xia Q, Zhu S, Wu Y, Wang J, Cai Y, Chen P, Li J, Heng BC, Ouyang HW, Lu P (2015) Intra-articular transplantation of atsttrin-transduced mesenchymal stem cells ameliorate osteoarthritis development. Stem Cells Transl Med 4:523–531Google Scholar
  162. Xu X, Shi D, Liu Y, Shen Y, Xu Z, Dai J, Chen D, Teng H, Jiang Q (2016) Synovium-derived mesenchymal stem cell sheet enhance autologous osteochondral transplantation in a rabbit model. Int J Clin Exp Med 9:10322–10332Google Scholar
  163. Xu X, Shi D, Liu Y, Yao Y, Dai J, XU Z, Chen D, Teng H, Jiang Q (2017) In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model. Exp Ther Med 14:239–245Google Scholar
  164. Yamagata M, Yamamoto A, Kako E, Kaneko N, Matsubara K, Sakai K, Sawamoto K, Ueda M (2013) Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke 44:551–554Google Scholar
  165. Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, Zhang X, Kiyan W, Kuroki H (2016) The effect of exercise on the early stages of mesenchymal stromal cell-induced cartilage repair in a rat osteochondral defect model. PLoS One 11:e0151580Google Scholar
  166. Yan H, Yu C (2007) Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23:178–187Google Scholar
  167. Yang D, Wang W, Li L, Peng Y, Chen P, Huang H, Guo Y, Xia X, Wang Y, Wang H, Wang WE, Zeng C (2013) The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair. PLoS One 8:e59020Google Scholar
  168. Yang X, Zhu TY, Wen LC, Cao YP, Liu C, Cui YP, Liu C, Cui YP, Meng ZC, Liu H (2015) Intraarticular injection of allogenic mesenchymal stem cells has a protective role for the osteoarthritis. Chin Med J 128:2516–2523Google Scholar
  169. Yun S, Ku SK, Kwon YS (2016) Adipose-derived mesenchymal stem cells and platelet-rich plasma synergistically ameliorate the surgical-induced osteoarthritis in Beagle dogs. J Orthop Surg 11:9Google Scholar
  170. Zellner J, Hierl K, Mueller M, Pfeifer C, Berner A, Dienstknecht T, Krutsch W, Geis S, Gehmert S, Kujat R, Dendorfer S, Prantl L, Nerlich M, Angele P (2013) Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone. J Biomed Mater Res B Appl Biomater 101:1133–1142Google Scholar
  171. Zellner J, Taeger CD, Schaffer M, Roldan JC, Loibl M, Mueller MB, Berner A, Krutsch W, Huber MK, Kujat R, Nerlich M, Angele P (2014) Are applied growth factors able to mimic the positive effects of mesenchymal stem cells on the regeneration of meniscus in the avascular zone? Biomed Res Int 2014:537686Google Scholar
  172. Zhang S, Jiang YZ, Zhang W, Chen L, Tong T, Liu W, Mu Q, Liu H, Ji J, Ouyang HW, Zou X (2013) Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression. Stem Cells Dev 22:90–101Google Scholar
  173. Zhang S, Chu WC, Lai RC, Lim SK, Hui JHP, Toh WS (2016a) Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthr Cartil 24:2135–2140Google Scholar
  174. Zhang W, Ouyang H, Dass CR, Xu J (2016b) Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4:15040Google Scholar
  175. Zhang ZZ, Wang SJ, Zhang JY, Jiang WB, Huang AB, Qi YS, Ding JX, Chen XS, Jiang D, Yu JK (2017) 3D-printed poly(ε-caprolactone) scaffold augmented with mesenchymal stem cells for total meniscal substitution: a 12- and 24-week animal study in a rabbit model. Am J Sports Med 45:1497–1511Google Scholar
  176. Zhu Y, Wu X, Liang Y, Gu H, Song K, Zou X, Zhou G (2016) Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes. BMC Biotechnol 16:78Google Scholar
  177. Zhu Y, Wang Y, Zhao B, Niu X, Hu B, Li Q, Zhang J, Ding J, Chen Y, Wang Y (2017) Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther 8:64Google Scholar
  178. Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J, Josten C, Bader A, Marquass B (2010) Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. Am J Sports Med 38:1857–1869Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Suleiman Alhaji Muhammad
    • 1
    • 2
  • Norshariza Nordin
    • 3
  • Muhammad Zulfadli Mehat
    • 4
  • Sharida Fakurazi
    • 1
    • 4
    Email author
  1. 1.Institute of BioscienceUniversiti Putra MalaysiaSerdangMalaysia
  2. 2.Department of BiochemistryUsmanu Danfodiyo UniversitySokotoNigeria
  3. 3.Department of Biomedical Science, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia
  4. 4.Department of Human Anatomy, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia

Personalised recommendations