Efficacy and safety of mesenchymal stem cell injections for patients with osteoarthritis: a meta-analysis and review of RCTs



Osteoarthritis (OA), which has a high incidence in the elderly, brings a huge economic burden to society. MSCs (Mesenchymal Stem Cells) have shown great multidirectional differentiation potential which are expected to treat OA, and numerous clinical trials have been conducted. However, the efficacy and safety of the MSCs still need to be further integrated and analyzed.

Materials and methods

We searched several databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, Ovid, and ScienceDirect) for assessing eligible trials that randomized controlled trials, hyaluronic acid as control, and MSCs injection to treat OA. Vitro studies and animal studies were excluded. Search terms were: “cartilage,” “clinical trial,” “mesenchymal,” “stromal” and “stem cell”, “osteoarthritis”. The preliminary guidelines and study protocol were published online at PROSPERO.


Many assessment scales could not be improved significantly after 6 months. However, most of the scales were significantly improved after 12 months, indicating that compared with hyaluronic acid, stem cells could relieve OA symptoms significantly. No serious adverse effect was found.


There are significant therapeutic effects on joint function, symptoms, and no permanent adverse effect has been found after stem cell treatment. It is promising to apply intro-articular injection of stem cells for OA to clinical application. More researches are needed to supplement present deficiencies.

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  1. 1.

    Bijlsma JWJ, Berenbaum F, Lafeber FPJG (2011) Osteoarthritis: an update with relevance for clinical practice. Lancet 377(9783):2115–2126. https://doi.org/10.1016/S0140-6736(11)60243-2

    Article  PubMed  Google Scholar 

  2. 2.

    Lin J, Fransen M, Kang X, Li H, Ke Y, Wang Z, Zhang Y, Su S (2010) Marked disability and high use of nonsteroidal antiinflammatory drugs associated with knee osteoarthritis in rural China: a cross-sectional population-based survey. Arthr Res Ther 12(6):R225. https://doi.org/10.1186/ar3212

    Article  Google Scholar 

  3. 3.

    Strotman PK, Novicoff WM, Nelson SJ, Browne JA (2019) Increasing public interest in stem cell injections for osteoarthritis of the hip and knee: a google trends analysis. J Arthroplast 34(6):1053–1057. https://doi.org/10.1016/j.arth.2019.03.002

    Article  Google Scholar 

  4. 4.

    Reisbig NA, Pinnell E, Scheuerman L, Hussein H, Bertone AL (2019) Synovium extra cellular matrices seeded with transduced mesenchymal stem cells stimulate chondrocyte maturation in vitro and cartilage healing in clinically-induced rat-knee lesions in vivo. PLoS ONE 14(3):e0212664. https://doi.org/10.1371/journal.pone.0212664

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084

    CAS  Article  Google Scholar 

  6. 6.

    Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822. https://doi.org/10.1182/blood-2004-04-1559

    CAS  Article  Google Scholar 

  7. 7.

    Harrell CR, Markovic BS, Fellabaum C, Arsenijevic A, Volarevic V (2019) Mesenchymal stem cell-based therapy of osteoarthritis: current knowledge and future perspectives. Biomed Pharmacother 109:2318–2326. https://doi.org/10.1016/j.biopha.2018.11.099

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Kuah D, Sivell S, Longworth T, James K, Guermazi A, Cicuttini F, Wang Y, Craig S, Comin G, Robinson D, Wilson J (2018) Safety, tolerability and efficacy of intra-articular Progenza in knee osteoarthritis: a randomized double-blind placebo-controlled single ascending dose study. J Transl Med. https://doi.org/10.1186/s12967-018-1420-z

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Domev H, Amit M, Laevsky I, Dar A, Itskovitz-Eldor J (2012) Efficient engineering of vascularized ectopic bone from human embryonic stem cell-derived mesenchymal stem cells. Tissue Eng Part A 18(21–22):2290–2302. https://doi.org/10.1089/ten.tea.2011.0371

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Horie M, Choi H, Lee RH, Reger RL, Ylostalo J, Muneta T, Sekiya I, Prockop DJ (2012) 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(10):1197–1207. https://doi.org/10.1016/j.joca.2012.06.002

    CAS  Article  PubMed Central  Google Scholar 

  11. 11.

    Wang H, Yan X, Jiang Y, Wang Z, Li Y, Shao Q (2018) The human umbilical cord stem cells improve the viability of OA degenerated chondrocytes. Mol Med Rep 17(3):4474–4482. https://doi.org/10.3892/mmr.2018.8413

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Song JS, Hong KT, Kim NM, Park HS, Choi NH (2020) Human umbilical cord blood-derived mesenchymal stem cell implantation for osteoarthritis of the knee. Arch Orthop Trauma Surg 140(4):503–509. https://doi.org/10.1007/s00402-020-03349-y

    Article  PubMed  Google Scholar 

  13. 13.

    Trujillo S, Henao J, Marín G, Isaza C, Vargas C, Aranzazu J, Murillo B, Isaza J, Marín C (2019) Stem cells doses in knee osteoarthritis. Cytotherapy 21(5):S55–S56. https://doi.org/10.1016/j.jcyt.2019.03.427

    Article  Google Scholar 

  14. 14.

    Hyunchul C, Chai JW, Jeong EC, Oh S, Shin JS, Shim H, Yoon KS (2017) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee a 2-year follow-up study. Am J Sports Med 45(12):2774–2783. https://doi.org/10.1177/0363546517716641

    Article  Google Scholar 

  15. 15.

    Emadedin M, Labibzadeh N, Liastani MG, Karimi A, Jaroughi N, Bolurieh T, Hosseini S-E, Baharvand H, Aghdami N (2018) Intra-articular implantation of autologous bone marrow-derived mesenchymal stromal cells to treat knee osteoarthritis: a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial. Cytotherapy 20(10):1238–1246. https://doi.org/10.1016/j.jcyt.2018.08.005

    Article  PubMed  Google Scholar 

  16. 16.

    Gobbi A, Whyte GP (2019) Long-term clinical outcomes of one-stage cartilage repair in the knee with hyaluronic acid-based scaffold embedded with mesenchymal stem cells sourced from bone marrow aspirate concentrate. Am J Sports Med 47(7):1621–1628. https://doi.org/10.1177/0363546519845362

    Article  PubMed  Google Scholar 

  17. 17.

    Hochberg MC (2000) Role of intra-articular hyaluronic acid preparations in medical management of osteoarthritis of the knee. Semin Arthritis Rheum 30(2 Suppl 1):2

    CAS  Article  Google Scholar 

  18. 18.

    Vega A, Martín-Ferrero MA, Canto FD, Alberca M, García V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sánchez A, García-Sancho J (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99(8):1681–1690. https://doi.org/10.1097/TP.0000000000000678

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Sanchez-Echenique C, Bondia JM, Aquerreta JD, Andreu EJ, Ornilla E, Villaron EM, Valenti-Azcarate A, Sanchez-Guijo F, Del Canizo MC, Valenti-Nin JR, Prosper F (2016) Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med 14(1):246. https://doi.org/10.1186/s12967-016-0998-2

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH (2013) Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy 29(12):2020–2028. https://doi.org/10.1016/j.arthro.2013.09.074

    Article  PubMed  Google Scholar 

  21. 21.

    Goncars V, Jakobsons E, Blums K, Briede I, Patetko L, Erglis K, Erglis M, Kalnberzs K, Muiznieks I, Erglis A (2017) The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections. Medicina-Lithuania 53(2):101–108. https://doi.org/10.1016/j.medici.2017.02.002

    Article  Google Scholar 

  22. 22.

    Wang Y, Jin W, Liu H, Cui Y, Mao Q, Fei Z, Xiang C (2016) Curative effect of human umbilical cord mesenchymal stem cells by intro-articular injection for degenerative knee osteoarthritis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 30(12):1472–1477. https://doi.org/10.7507/1002-1892.20160305

    Article  PubMed  Google Scholar 

  23. 23.

    Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, Alcayaga-Miranda F, González PL, Muse E, Khoury M, Figueroa EF, Espinoza F (2019) Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: repeated MSC dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized phase I/II trial. Stem cells Transl Med 8(3):215–224. https://doi.org/10.1002/sctm.18-0053

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Turajane T, Chaveewanakorn U, Fongsarun W, Aojanepong J, Papadopoulos KI (2017) Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial with differential effects of growth factor addition. Stem Cells Int. https://doi.org/10.1155/2017/8925132

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Saw K-Y, Anz A, Siew-Yoke Jee C, Merican S, Ching-Soong Ng R, Roohi SA, Ragavanaidu K (2013) Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthrosc J Arthrosc Relat Surg 29(4):684–694. https://doi.org/10.1016/j.arthro.2012.12.008

    Article  Google Scholar 

  26. 26.

    Lu L, Dai C, Zhang Z, Du H, Li S, Ye P, Fu Q, Zhang L, Wu X, Dong Y, Song Y, Zhao D, Pang Y, Bao C (2019) Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem Cell Res Ther. https://doi.org/10.1186/s13287-019-1248-3

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Koenig KM, Ong KL, Lau EC, Vail TP, Berry DJ, Rubash HE, Kurtz S, Bozic KJ (2016) The use of hyaluronic acid and corticosteroid injections among medicare patients with knee osteoarthritis. J Arthroplast 31(2):351–355. https://doi.org/10.1016/j.arth.2015.08.024

    Article  Google Scholar 

  28. 28.

    Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, Ayeni OR, Bhandari M (2012) Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am 94(4):298–307. https://doi.org/10.2106/JBJS.K.00154

    Article  PubMed  Google Scholar 

  29. 29.

    Oprenyeszk F, Sanchez C, Dubuc J-E, Maquet V, Henrist C, Compère P, Henrotin Y (2015) Chitosan enriched three-dimensional matrix reduces inflammatory and catabolic mediators production by human chondrocytes. PLoS ONE 10(5):e0128362. https://doi.org/10.1371/journal.pone.0128362

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Henriksen M, Hansen JB, Klokker L, Bliddal H, Christensen R (2016) Comparable effects of exercise and analgesics for pain secondary to knee osteoarthritis: a meta-analysis of trials included in Cochrane systematic reviews. J Comp Eff Res 5(4):417–431. https://doi.org/10.2217/cer-2016-0007

    Article  PubMed  Google Scholar 

  31. 31.

    Zeng C, Dubreuil M, LaRochelle MR, Lu N, Wei J, Choi HK, Lei G, Zhang Y (2019) Association of tramadol with all-cause mortality among patients with osteoarthritis. JAMA 321(10):969–982. https://doi.org/10.1001/jama.2019.1347

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    De Lucia O, Murgo A, Pregnolato F, Pontikaki I, De Souza M, Sinelli A, Cimaz R, Caporali R (2020) Hyaluronic acid injections in the treatment of osteoarthritis secondary to primary inflammatory rheumatic diseases: a systematic review and qualitative synthesis. Adv Ther 37(4):1347–1359. https://doi.org/10.1007/s12325-020-01256-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Skou ST, Roos EM (2019) Physical therapy for patients with knee and hip osteoarthritis: supervised, active treatment is current best practice. Clin Exp Rheumatol 120(5):112–117

    Google Scholar 

  34. 34.

    Anderson ML, Allen KD, Golightly YM, Arbeeva LS, Goode A, Huffman KM, Schwartz TA, Hill CH (2019) Fall risk and utilization of balance training for adults with symptomatic knee osteoarthritis: secondary analysis from a randomized clinical trial. J Geriatr Phys Ther 42(2):E39–E44. https://doi.org/10.1519/JPT.0000000000000213

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Nixon AJ, Grol MW, Lang HM, Ruan MZC, Stone A, Begum L, Chen Y, Dawson B, Gannon F, Plutizki S, Lee BHL, Guse K (2018) Disease-modifying osteoarthritis treatment with interleukin-1 receptor antagonist gene therapy in small and large animal models. Arthr Rheumatol 70(11):1757–1768. https://doi.org/10.1002/art.40668

    CAS  Article  Google Scholar 

  36. 36.

    Vinatier C, Bouffi C, Merceron C, Gordeladze J, Brondello J-M, Jorgensen C, Weiss P, Guicheux J, Noël D (2009) Cartilage tissue engineering: towards a biomaterial-assisted mesenchymal stem cell therapy. Curr Stem Cell Res Ther 4(4):318–329

    CAS  Article  Google Scholar 

  37. 37.

    Kim H-J, Im G-I (2009) Combination of transforming growth factor-beta2 and bone morphogenetic protein 7 enhances chondrogenesis from adipose tissue-derived mesenchymal stem cells. Tissue Eng Part A 15(7):1543–1551. https://doi.org/10.1089/ten.tea.2008.0368

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Mastrogiacomo M, Derubeis AR, Cancedda R (2005) Bone and cartilage formation by skeletal muscle derived cells. J Cell Physiol 204(2):594–603

    CAS  Article  Google Scholar 

  39. 39.

    Uzieliene I, Urbonaite G, Tachtamisevaite Z, Mobasheri A, Bernotiene E (2018) The potential of menstrual blood-derived mesenchymal stem cells for cartilage repair and regeneration: novel aspects. Stem Cells Int 2018:5748126. https://doi.org/10.1155/2018/5748126

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Koga H, Muneta T, Nagase T, Nimura A, Ju YJ, Mochizuki T, Sekiya I (2008) Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res 333(2):207–215. https://doi.org/10.1007/s00441-008-0633-5

    Article  PubMed  Google Scholar 

  41. 41.

    Koh YG, Choi YJ (2012) Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 19(6):902–907. https://doi.org/10.1016/j.knee.2012.04.001

    Article  PubMed  Google Scholar 

  42. 42.

    Dubey NK, Wei H-J, Yu S-H, Williams DF, Wang JR, Deng Y-H, Tsai F-C, Wang PD, Deng W-P (2019) Adipose-derived stem cells attenuates diabetic osteoarthritis via inhibition of glycation-mediated inflammatory cascade. Aging Dis 10(3):483–496. https://doi.org/10.14336/AD.2018.0616

    Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, Paterson K, Boyd R (2019) Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med 14(3):213–230. https://doi.org/10.2217/rme-2018-0161

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Doyle EC, Wragg NM, Wilson SL (2020) Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. https://doi.org/10.1007/s00167-020-05859-z

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Xu T, Yu X, Yang Q, Liu X, Fang J, Dai X (2019) Autologous micro-fragmented adipose tissue as stem cell-based natural scaffold for cartilage defect repair. Cell Transplant 28(12):1709–1720. https://doi.org/10.1177/0963689719880527

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Riegger J, Brenner RE (2020) Pathomechanisms of posttraumatic osteoarthritis: chondrocyte behavior and fate in a precarious environment. Int J Mol Sci. https://doi.org/10.3390/ijms21051560

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Liu-Bryan R, Terkeltaub R (2015) Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11(1):35–44. https://doi.org/10.1038/nrrheum.2014.162

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Ng J, Little CB, Woods S, Whittle S, Lee FY, Gronthos S, Mukherjee S, Hunter DJ, Worthley DL (2020) Stem cell-directed therapies for osteoarthritis: the promise and the practice. Stem cells (Dayton, Ohio) 38(4):477–486. https://doi.org/10.1002/stem.3139

    Article  Google Scholar 

  49. 49.

    Schmal H, Mehlhorn A, Stoffel F, Köstler W, Südkamp NP, Niemeyer P (2009) In vivo quantification of intraarticular cytokines in knees during natural and surgically induced cartilage repair. Cytotherapy 11(8):1065–1075. https://doi.org/10.3109/14653240903219130

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Song SY, Hong J, Go S, Lim S, Sohn HS, Kang M, Jung G-J, Yoon J-K, Kang ML, Im G-I, Kim B-S (2020) Interleukin-4 gene transfection and spheroid formation potentiate therapeutic efficacy of mesenchymal stem cells for osteoarthritis. Adv Healthcare Mater 9(5):e1901612. https://doi.org/10.1002/adhm.201901612

    CAS  Article  Google Scholar 

  51. 51.

    Siegel G, Schäfer R, Dazzi F (2009) The immunosuppressive properties of mesenchymal stem cells. Transplantation 87(9S):S45–S49. https://doi.org/10.1097/TP.0b013e3181a285b0

    Article  PubMed  Google Scholar 

  52. 52.

    Casado JG, Blazquez R, Vela FJ, Alvarez V, Tarazona R, Sanchez-Margallo FM (2017) Mesenchymal stem cell-derived exosomes: immunomodulatory evaluation in an antigen-induced synovitis porcine model. Front Vet Sci 4:39. https://doi.org/10.3389/fvets.2017.00039

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D (2017) Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep 7(1):16214. https://doi.org/10.1038/s41598-017-15376-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Hsu C-C, Cheng J-H, Wang C-J, Ko J-Y, Hsu S-L, Hsu T-C (2020) Shockwave therapy combined with autologous adipose-derived mesenchymal stem cells is better than with human umbilical cord wharton’s jelly-derived mesenchymal stem cells on knee osteoarthritis. Int J Mol Sci. https://doi.org/10.3390/ijms21041217

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Koh RH, Jin Y, Kim J, Hwang NS (2020) Inflammation-modulating hydrogels for osteoarthritis cartilage tissue engineering. Cells. https://doi.org/10.3390/cells9020419

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Xu S, Liu H, Xie Y, Sang L, Liu J, Chen B (2015) Effect of mesenchymal stromal cells for articular cartilage degeneration treatment: a meta-analysis. Cytotherapy 17(10):1342–1352. https://doi.org/10.1016/j.jcyt.2015.05.005

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Kim SH, Ha C-W, Park Y-B, Nam E, Lee J-E, Lee H-J (2019) Intra-articular injection of mesenchymal stem cells for clinical outcomes and cartilage repair in osteoarthritis of the knee: a meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg 139(7):971–980. https://doi.org/10.1007/s00402-019-03140-8

    Article  PubMed  Google Scholar 

  58. 58.

    Goncars V, Kalnberzs K, Jakobsons E, Engele I, Briede I, Blums K, Erglis K, Erglis M, Patetko L, Muiznieks I, Erglis A (2019) Treatment of knee osteoarthritis with bone marrow-derived mononuclear cell injection: 12-month follow-up. Cartilage 10(1):26–35. https://doi.org/10.1177/1947603517746721

    Article  PubMed  Google Scholar 

  59. 59.

    Zhang BY, Wang BY, Li SC, Luo DZ, Zhan X, Chen SF, Chen ZS, Liu CY, Ji HQ, Bai YS, Li DS, He Y (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. https://doi.org/10.1155/2018/1983025

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Jiang B, Fu X, Yan L, Li S, Zhao D, Wang X, Duan Y, Yan Y, Li E, Wu K, Inglis BM, Ji W, Xu RH, Si W (2019) Transplantation of human ESC-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques. Theranostics 9(22):6587–6600. https://doi.org/10.7150/thno.35391

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Varma HS, Dadarya B, Vidyarthi A (2010) The new avenues in the management of osteo-arthritis of knee–stem cells. J Indian Med Assoc 108(9):583–585

    CAS  PubMed  Google Scholar 

  62. 62.

    Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M (2002) Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthr Cartil 10(3):199–206

    CAS  Article  Google Scholar 

  63. 63.

    Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R (2016) A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop 40(8):1755–1765. https://doi.org/10.1007/s00264-016-3162-y

    Article  PubMed  Google Scholar 

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This study was funded by Youth Medical Key Talent Project of Jiangsu (QNRC2016844) and the eighteenth batch of scientific research projects of Jiangsu University (18A509).

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Conceptualization: PJ. Data collection: PJ and LM. Project administration: DL. Methodology: QZ and LQ. Formal analysis: QZ and LM. Funding acquisition: DL and PJ. Investigation: XL. Software: PJ and XL. Resources: PJ and LM. Supervision: DL. Validation: QZ. Visualization: PJ. Writing ± original draft: PJ. Writing ± review and editing: DL and QZ.

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Correspondence to Dapeng Li.

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All the authors declare that they have no conflict of interest. The authors thank MD Chao Shen for his contributions to this scientific work and Dr. Abdulraheem Gul for his contributions to language improvement.

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Jiang, P., Mao, L., Qiao, L. et al. Efficacy and safety of mesenchymal stem cell injections for patients with osteoarthritis: a meta-analysis and review of RCTs. Arch Orthop Trauma Surg (2021). https://doi.org/10.1007/s00402-020-03703-0

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  • Mesenchymal stem cells
  • Osteoarthritis
  • Therapy
  • Adverse effects