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LO SCALPELLO-OTODI Educational

, Volume 33, Issue 3, pp 237–242 | Cite as

Le cellule staminali: impiego clinico

  • F. VandenbulckeEmail author
  • G. Beltrame
  • N. D. Vitale
  • B. Di Matteo
  • E. Kon
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The clinical application of MSCs in orthopaedics

Abstract

A systematic review of clinical applications of MSCs in the treatment of knee osteoarthritis (OA). Twenty-three papers were included in the final analysis (10 on BMAC and 13 on SVF). Of these, only 4 were randomised controlled trials (RCTs). The Coleman Score, used for bias risk evaluation, revealed an overall poor quality of the studies. In terms of clinical application, despite the apparent safety and the short-term positive clinical outcomes, clinicians reported different preparation and administration methods. The available literature is not sufficient to make any recommendation on the use of either product in clinical practice, even though they have both shown to be safe and have some short-term beneficial effects.

Notes

Conflitto di interesse

Gli autori F. Vandenbulcke, G. Beltrame, N.D. Vitale, B. Di Matteo e E. Kon dichiarano di non avere alcun conflitto di interesse.

Consenso informato e conformità agli standard etici

Tutte le procedure descritte nello studio e che hanno coinvolto esseri umani sono state attuate in conformità alle norme etiche stabilite dalla dichiarazione di Helsinki del 1975 e successive modifiche. Il consenso informato è stato ottenuto da tutti i pazienti inclusi nello studio.

Human and Animal Rights

L’articolo non contiene alcuno studio eseguito su esseri umani e su animali da parte degli autori.

Bibliografia

  1. 1.
    Poole AR (2003) What type of cartilage repair are we attempting to attain? J Bone Jt Surg, Am 85-A(Suppl):40–44 Google Scholar
  2. 2.
    Richards MM, Maxwell JS, Weng L et al. (2016) Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed 44(2):101–108 PubMedPubMedCentralGoogle Scholar
  3. 3.
    Heijink A, Gomoll AH, Madry H et al. (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20(3):423–435 PubMedGoogle Scholar
  4. 4.
    Vos T, Flaxman AD, Naghavi M et al. (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2163–2196 PubMedPubMedCentralGoogle Scholar
  5. 5.
    Yoshimura K, Shigeura T, Matsumoto D et al. (2006) Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. J Cell Physiol 208(1):64–76 PubMedGoogle Scholar
  6. 6.
    Verbus EA, Kenyon JD, Sergeeva O et al. (2017) Expression of miR-145-5p during chondrogenesis of mesenchymal stem cells. J Stem Cell Res (Overl Park) 1(3):1–10 Google Scholar
  7. 7.
    DiMarino AM, Caplan AI, Bonfield TL (2013) Mesenchymal stem cells in tissue repair. Front Immunol 4:201 PubMedPubMedCentralGoogle Scholar
  8. 8.
    Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213(2):341–347 PubMedPubMedCentralGoogle Scholar
  9. 9.
    Wu L, Cai X, Zhang S et al. (2013) Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine. J Cell Physiol 228(5):938–944 PubMedGoogle Scholar
  10. 10.
    Filardo G, Madry H, Jelic M et al. (2013) Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc 21(8):1717–1729 PubMedGoogle Scholar
  11. 11.
    US Food and Drug Administration (2018) Regulatory considerations for human cells, tissues, and cellular and tissue-based products: minimal manipulation and homologous use. Guidance for industry and Food and Drug Administration Staff www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM585403.pdf. Accessed February 2018
  12. 12.
    de Girolamo L, Kon E, Filardo G et al. (2016) Regenerative approaches for the treatment of early OA. Knee Surg Sports Traumatol Arthrosc 24(6):1826–1835 PubMedGoogle Scholar
  13. 13.
    Pak J, Lee J, Pak N et al. (2018) Cartilage regeneration in humans with adipose tissue-derived stem cells and adipose stromal vascular fraction cells: updated status. Int J Mol Sci 19(7):2146 PubMedCentralGoogle Scholar
  14. 14.
    Moher D, Liberati A, Tetzlaff J, Altman DG (the PRISMA Group) (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097 PubMedPubMedCentralGoogle Scholar
  15. 15.
    Kon E, Verdonk P, Condello V (2009) Matrix-assisted autologous chondrocyte transplantation for the repair of cartilage defects of the knee systematic clinical data review. Am J Sports Med 2009:156–166 Google Scholar
  16. 16.
    Themistocleous GS, Chloros GD, Kyrantzoulis IM et al.(2018) Effectiveness of a single intra-articular bone marrow aspirate concentrate (BMAC) injection in patients with grade 3 and 4 knee osteoarthritis. Heliyon 4(10):e00871 PubMedPubMedCentralGoogle Scholar
  17. 17.
    Shaw B, Darrow M, Derian A (2018) Short-term outcomes in treatment of knee osteoarthritis with 4 bone marrow concentrate injections. Clin Med Insights Arthritis Musculoskelet Disord.  https://doi.org/10.1177/1179544118781080 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Rodriguez-Fontan F, Piuzzi NS, Kraeutler MJ, Pascual-Garrido C (2018) Early clinical outcomes of intra-articular injections of bone marrow aspirate concentrate for the treatment of early osteoarthritis of the hip and knee: a cohort study. Phys Med Rehabil J 10(12):1353–1359 Google Scholar
  19. 19.
    Shapiro SA, Arthurs JR, Heckman MG et al. (2019) Quantitative T2 MRI mapping and 12-month follow-up in a randomized, blinded, placebo controlled trial of bone marrow aspiration and concentration for osteoarthritis of the knees. Cartilage 10(4):432–443 PubMedGoogle Scholar
  20. 20.
    Sampson S, Vincent H, Aufiero D (2016) Intra-articular bone marrow concentrate injection protocol: short-term efficacy in osteoarthritis. Regen Med 11:511–520 PubMedGoogle Scholar
  21. 21.
    Centeno CJ, Al-Sayegh H, Bashir J et al. (2015) A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord 16:258 PubMedPubMedCentralGoogle Scholar
  22. 22.
    Centeno C, Pitts J, Al-Sayegh H, Freeman M (2014) Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft. BioMed Res Int 2014:370621 PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kim J-D, Lee GW, Jung GH et al. (2014) Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee. Eur J Orthop Surg Traumatol 24:1505–1511 PubMedGoogle Scholar
  24. 24.
    Vad V, Barve R, Linnell E, Harrison J (2016) Knee osteoarthritis treated with percutaneous chondral-bone interface optimization: a pilot trial. Surg Sci 7:1–12 Google Scholar
  25. 25.
    Hernigou P, Auregan JC, Dubory A et al. (2018) Subchondral stem cell therapy versus controlateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Int Orthop 42:2563–2571 PubMedGoogle Scholar
  26. 26.
    Hudetz D, Bori I, Rod E et al. (2017) The effect of intra-articular injection of autologous microfragmented fat tissue on proteoglycan synthesis in patients with knee osteoarthritis. Genes (Basel) 8(10):E270 Google Scholar
  27. 27.
    Yokota N, Yamakawa M, Shirata T, Kimura T (2017) Clinical results following intra-articular injection of adipose-derived stromal vascular fraction cells in patients with osteoarthritis of the knee. Regen Ther 6:108–112 PubMedPubMedCentralGoogle Scholar
  28. 28.
    Jones IA, Wilson M, Togashi R et al. (2018) A randomized, controlled study to evaluate the efficacy of intra-articular, autologous adipose tissue injections for the treatment of mild-to-moderate knee osteoarthritis compared to hyaluronic acid: a study protocol. BMC Musculoskelet Disord 19(1):383 PubMedPubMedCentralGoogle Scholar
  29. 29.
    Roato I, Belisario DC, Compagno M et al. (2018) Concentrated adipose tissue infusion for the treatment of knee osteoarthritis: clinical and histological observations. Int Orthop 43(1):15–23 PubMedGoogle Scholar
  30. 30.
    Bansal H, Comella K, Leon J et al. (2017) Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis. J Transl Med 15(1):141 PubMedPubMedCentralGoogle Scholar
  31. 31.
    Bui KH, Duong TD, Nguyen NT et al. (2014) Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomed Res Ther 2014(1):02 Google Scholar
  32. 32.
    Koh Y, Kwon O, Kim Y, Choi Y (2014) Comparative outcomes of open-wedge high tibial osteotomy mesenchymal stem cell treatment: a prospective study. Arthroscopy 30(11):1453–1460 PubMedGoogle Scholar
  33. 33.
    Hong Z, Chen J, Zhang S et al. (2018) Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial. Int Orthop 43(5):1123–1134 PubMedGoogle Scholar
  34. 34.
    Kim YS, Hospital YS, Suh DS et al. (2015) Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold? Am J Sports Med 43(1):176–185 PubMedGoogle Scholar
  35. 35.
    Koh YG, Choi YJ, Kwon OR (2014) Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med 42(7):1628–1637 PubMedGoogle Scholar
  36. 36.
    Kwon YK (2013) Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 23(5):1308–1316 PubMedGoogle Scholar
  37. 37.
    Nguyen PD, Tran TD-X, Nguyen HT-N et al. (2016) Comparative clinical observation of arthroscopic microfracture in the presence and absence of a stromal vascular fraction injection for osteoarthritis. Stem Cells Transl Med 6:187–195 PubMedPubMedCentralGoogle Scholar
  38. 38.
    Koh Y-G, Jo S-B, Kwon O-R et al. (2013) Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 29(4):748–755 PubMedPubMedCentralGoogle Scholar
  39. 39.
    Di Matteo B, Kon E (2019) Editorial commentary: biologic products for cartilage regeneration—time to redefine the rules of the game? Arthroscopy 35(1):260–261 PubMedGoogle Scholar
  40. 40.
    Hadley CJ, Shi WJ, Murphy H et al. (2019) The clinical evidence behind biologic therapies promoted at annual orthopaedic meetings: a systematic review. Arthroscopy 35(1):251–259 PubMedGoogle Scholar
  41. 41.
    Di Matteo B, Marcacci M, Kon E (2018) Letter to the editor concerning the article: “Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial” (Hong et al. International Orthopaedics doi:10.1007/s00264-018-4099-0). Int Orthop 43(3):751–752 PubMedGoogle Scholar
  42. 42.
    Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100(9):1249–1260 PubMedPubMedCentralGoogle Scholar
  43. 43.
    Zuk PA, Zhu M, Ashjian P et al. (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295 PubMedPubMedCentralGoogle Scholar
  44. 44.
    Aust L, Devlin B, Foster SJ et al. (2004) Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy 6(1):7–14 PubMedGoogle Scholar
  45. 45.
    Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M et al. (2006) Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy 8(2):166–177 PubMedGoogle Scholar
  46. 46.
    Vezzani B, Shaw I, Lesme H et al. (2018) Higher pericyte content and secretory activity of microfragmented human adipose tissue compared to enzymatically derived stromal vascular fraction. Stem Cells Transl Med 2018:876–886 Google Scholar

Copyright information

© Società Italiana Ortopedici Traumatologi Ospedalieri d’Italia 2019

Authors and Affiliations

  • F. Vandenbulcke
    • 1
    • 2
    Email author
  • G. Beltrame
    • 1
  • N. D. Vitale
    • 1
    • 2
  • B. Di Matteo
    • 1
    • 2
  • E. Kon
    • 1
    • 2
    • 3
  1. 1.Department of Biomedical SciencesHumanitas UniversityRozzano (MI)Italia
  2. 2.Humanitas Clinical and Research CenterRozzano (MI)Italia
  3. 3.First Moscow State Medical University – Sechenov UniversityMoscaRussia

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