Stem cells in articular cartilage regeneration

Giuseppe Filardo, Francesco Perdisa, Alice Roffi, Maurilio Marcacci, Elizaveta Kon, Giuseppe Filardo, Francesco Perdisa, Alice Roffi, Maurilio Marcacci, Elizaveta Kon

Abstract

Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.

Figures

Fig. 1
Fig. 1
Scheme of research methodology
Fig. 2
Fig. 2
The systematic research showed an increasing number of clinical studies published over time

References

    1. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58:15–25. doi: 10.1002/art.23177.
    1. Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185–99. doi: 10.1093/bmb/lds038.
    1. Di Martino A, Kon E, Perdisa F, Sessa A, Filardo G, Neri MP, Bragonzoni L, Marcacci M. Surgical treatment of early knee osteoarthritis with a cell-free osteochondral scaffold: results at 24 months of follow-up. Injury. 2015;46(Suppl 8):S33–8. doi: 10.1016/S0020-1383(15)30052-8.
    1. Kon E, Filardo G, Drobnic M, Madry H, Jelic M, van Dijk N, Della Villa S. Non-surgical management of early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012;20:436–49. doi: 10.1007/s00167-011-1713-8.
    1. Kon E, Filardo G, Roffi A, Andriolo L, Marcacci M. New trends for knee cartilage regeneration: from cell-free scaffolds to mesenchymal stem cells. Curr Rev Musculoskelet Med. 2012;5:236–43. doi: 10.1007/s12178-012-9135-x.
    1. Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E. Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc. 2013;21:1717–29. doi: 10.1007/s00167-012-2329-3.
    1. Manferdini C, Maumus M, Gabusi E, Piacentini A, Filardo G, Peyrafitte JA, Jorgensen C, Bourin P, Fleury-Cappellesso S, Facchini A, et al. Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis Rheum. 2013;65:1271–81. doi: 10.1002/art.37908.
    1. Caplan AI. All MSCs are pericytes? Cell Stem Cell. 2008;3:229–30. doi: 10.1016/j.stem.2008.08.008.
    1. Caplan AI. New era of cell-based orthopedic therapies. Tissue Eng Part B Rev. 2009;15:195–200. doi: 10.1089/ten.teb.2008.0515.
    1. Perdisa F, Gostynska N, Roffi A, Filardo G, Marcacci M, Kon E. Adipose-derived mesenchymal stem cells for the treatment of articular cartilage: a systematic review on preclinical and clinical evidence. Stem Cells Int. 2015;2015:597652. doi: 10.1155/2015/597652.
    1. Ahmed TA, Hincke MT. Mesenchymal stem cell-based tissue engineering strategies for repair of articular cartilage. Histol Histopathol. 2014;29:669–89.
    1. Berg L, Koch T, Heerkens T, Bessonov K, Thomsen P, Betts D. Chondrogenic potential of mesenchymal stromal cells derived from equine bone marrow and umbilical cord blood. Vet Comp Orthop Traumatol. 2009;22:363–70.
    1. Kotobuki N, Hirose M, Takakura Y, Ohgushi H. Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow. Artif Organs. 2004;28:33–9. doi: 10.1111/j.1525-1594.2004.07320.x.
    1. Sensebe L, Krampera M, Schrezenmeier H, Bourin P, Giordano R. Mesenchymal stem cells for clinical application. Vox Sang. 2010;98:93–107. doi: 10.1111/j.1423-0410.2009.01227.x.
    1. Indrawattana N, Chen G, Tadokoro M, Shann LH, Ohgushi H, Tateishi T, Tanaka J, Bunyaratvej A. Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem Biophys Res Commun. 2004;320:914–9. doi: 10.1016/j.bbrc.2004.06.029.
    1. Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;11:343–53.
    1. Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011;14:211–5. doi: 10.1111/j.1756-185X.2011.01599.x.
    1. Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, Farjad R, Baghaban Eslaminejad M. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15:422–8.
    1. Rich S, Munar A, Soler Romagosa F, Peirau X, Huguet M, Alberca M, Sánchez A, García Sancho J, Orozco L. Treatment of knee osteoarthritis with autologous expanded bone marrow mesenchymal stem cells: 50 cases clinical and MRI results at one year follow-up. J Stem Cell Res Ther. 2015;5:7.
    1. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013;95:1535–41. doi: 10.1097/TP.0b013e318291a2da.
    1. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation. 2014;97:e66–8. doi: 10.1097/TP.0000000000000167.
    1. Davatchi F, Sadeghi Abdollahi B, Mohyeddin M, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis. 2015.
    1. Lee KB, Wang VT, Chan YH, Hui JH. A novel, minimally-invasive technique of cartilage repair in the human knee using arthroscopic microfracture and injections of mesenchymal stem cells and hyaluronic acid—a prospective comparative study on safety and short-term efficacy. Ann Acad Med Singapore. 2012;41:511–7.
    1. Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH. 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. 2013;29:2020–8. doi: 10.1016/j.arthro.2013.09.074.
    1. Vangsness CT, Jr, Farr J, 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014;96:90–8. doi: 10.2106/JBJS.M.00058.
    1. Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, et al. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation. 2015;99:1681–90. doi: 10.1097/TP.0000000000000678.
    1. Adachi N, Ochi M, Deie M, Ito Y. Transplant of mesenchymal stem cells and hydroxyapatite ceramics to treat severe osteochondral damage after septic arthritis of the knee. J Rheumatol. 2005;32:1615–8.
    1. Haleem AM, Singergy AA, Sabry D, Atta HM, Rashed LA, Chu CR, El Shewy MT, Azzam A, Abdel Aziz MT. The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results. Cartilage. 2010;1:253–61. doi: 10.1177/1947603510366027.
    1. Kasemkijwattana C, Hongeng S, Kesprayura S, Rungsinaporn V, Chaipinyo K, Chansiri K. Autologous bone marrow mesenchymal stem cells implantation for cartilage defects: two cases report. J Med Assoc Thai. 2011;94:395–400.
    1. Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K, Ohgushi H, Wakitani S, Kurosaka M. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007;15:226–31. doi: 10.1016/j.joca.2006.08.008.
    1. Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007;1:74–9. doi: 10.1002/term.8.
    1. Wakitani S, Mitsuoka T, Nakamura N, Toritsuka Y, Nakamura Y, Horibe S. Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Cell Transplant. 2004;13:595–600. doi: 10.3727/000000004783983747.
    1. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10:199–206. doi: 10.1053/joca.2001.0504.
    1. Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38:1110–6. doi: 10.1177/0363546509359067.
    1. Richter M, Zech S. Matrix-associated stem cell transplantation (MAST) in chondral defects of foot and ankle is effective. Foot Ankle Surg. 2013;19:84–90. doi: 10.1016/j.fas.2012.11.005.
    1. Varma HS, Dadarya B, Vidyarthi A. The new avenues in the management of osteo-arthritis of knee—stem cells. J Indian Med Assoc. 2010;108:583–5.
    1. Giannini S, Buda R, Vannini F, Cavallo M, Grigolo B. One-step bone marrow-derived cell transplantation in talar osteochondral lesions. Clin Orthop Relat Res. 2009;467:3307–20. doi: 10.1007/s11999-009-0885-8.
    1. Giannini S, Buda R, Battaglia M, Cavallo M, Ruffilli A, Ramponi L, Pagliazzi G, Vannini F. One-step repair in talar osteochondral lesions: 4-year clinical results and t2-mapping capability in outcome prediction. Am J Sports Med. 2013;41:511–8. doi: 10.1177/0363546512467622.
    1. Buda R, Cavallo M, Castagnini F, Cenacchi A, Natali S, Vannini F, Giannini S. Treatment of hemophilic ankle arthropathy with one-step arthroscopic bone marrow-derived cells transplantation. Cartilage. 2015;6:150–5. doi: 10.1177/1947603515574286.
    1. Buda R, Castagnini F, Cavallo M, Ramponi L, Vannini F, Giannini S. “One-step” bone marrow-derived cells transplantation and joint debridement for osteochondral lesions of the talus in ankle osteoarthritis: clinical and radiological outcomes at 36 months. Arch Orthop Trauma Surg. 2015.
    1. Buda R, Vannini F, Cavallo M, Baldassarri M, Natali S, Castagnini F, Giannini S. One-step bone marrow-derived cell transplantation in talarosteochondral lesions: mid-term results. Joints. 2013;1:102–7.
    1. Giannini S, Buda R, Cavallo M, Ruffilli A, Cenacchi A, Cavallo C, Vannini F. Cartilage repair evolution in post-traumatic osteochondral lesions of the talus: from open field autologous chondrocyte to bone-marrow-derived cells transplantation. Injury. 2010;41:1196–203. doi: 10.1016/j.injury.2010.09.028.
    1. Buda R, Vannini F, Castagnini F, Cavallo M, Ruffilli A, Ramponi L, Pagliazzi G, Giannini S. Regenerative treatment in osteochondral lesions of the talus: autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation. Int Orthop. 2015;39:893–900. doi: 10.1007/s00264-015-2685-y.
    1. Cadossi M, Buda RE, Ramponi L, Sambri A, Natali S, Giannini S. Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study. Foot Ankle Int. 2014;35:981–7. doi: 10.1177/1071100714539660.
    1. Buda R, Vannini F, Cavallo M, Grigolo B, Cenacchi A, Giannini S. Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells. J Bone Joint Surg Am. 2010;92(Suppl 2):2–11. doi: 10.2106/JBJS.J.00813.
    1. Buda R, Vannini F, Cavallo M, Baldassarri M, Luciani D, Mazzotti A, Pungetti C, Olivieri A, Giannini S. One-step arthroscopic technique for the treatment of osteochondral lesions of the knee with bone-marrow-derived cells: three years results. Musculoskelet Surg. 2013;97:145–51. doi: 10.1007/s12306-013-0242-7.
    1. Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-induced autologous chondrocyte implantation versus multipotent stem cells for the treatment of large patellofemoral chondral lesions: a nonrandomized prospective trial. Cartilage. 2015;6:82–97. doi: 10.1177/1947603514563597.
    1. Gigante A, Cecconi S, Calcagno S, Busilacchi A, Enea D. Arthroscopic knee cartilage repair with covered microfracture and bone marrow concentrate. Arthrosc Tech. 2012;1:e175–80. doi: 10.1016/j.eats.2012.07.001.
    1. Gigante A, Calcagno S, Cecconi S, Ramazzotti D, Manzotti S, Enea D. Use of collagen scaffold and autologous bone marrow concentrate as a one-step cartilage repair in the knee: histological results of second-look biopsies at 1 year follow-up. Int J Immunopathol Pharmacol. 2011;24:69–72.
    1. Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med. 2014;42:648–57. doi: 10.1177/0363546513518007.
    1. Skowronski J, Skowronski R, Rutka M. Large cartilage lesions of the knee treated with bone marrow concentrate and collagen membrane—results. Ortop Traumatol Rehabil. 2013;15:69–76. doi: 10.5604/15093492.1058409.
    1. Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CS, McGuire DA. Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy. 2011;27:493–506. doi: 10.1016/j.arthro.2010.11.054.
    1. Turajane T, Chaweewannakorn U, Larbpaiboonpong V, Aojanepong J, Thitiset T, Honsawek S, Fongsarun J, Papadopoulos KI. Combination of intra-articular autologous activated peripheral blood stem cells with growth factor addition/ preservation and hyaluronic acid in conjunction with arthroscopic microdrilling mesenchymal cell stimulation Improves quality of life and regenerates articular cartilage in early osteoarthritic knee disease. J Med Assoc Thai. 2013;96:580–8.
    1. Saw KY, Anz A, Siew-Yoke Jee C, Merican S, Ching-Soong Ng R, Roohi SA, Ragavanaidu K. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy. 2013;29:684–94. doi: 10.1016/j.arthro.2012.12.008.
    1. Fu WL, Ao YF, Ke XY, Zheng ZZ, Gong X, Jiang D, Yu JK. Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment. Knee. 2014;21:609–12. doi: 10.1016/j.knee.2013.10.010.
    1. Skowronski J, Skowronski R, Rutka M. Cartilage lesions of the knee treated with blood mesenchymal stem cells—results. Ortop Traumatol Rehabil. 2012;14:569–77.
    1. Koga H, Muneta T, Nagase T, Nimura A, Ju YJ, Mochizuki T, Sekiya I. Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res. 2008;333:207–15. doi: 10.1007/s00441-008-0633-5.
    1. Jang Y, Koh YG, Choi YJ, Kim SH, Yoon DS, Lee M, Lee JW. Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration. In Vitro Cell Dev Biol Anim. 2015;51:142–50. doi: 10.1007/s11626-014-9814-6.
    1. Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 2014;32:1254–66. doi: 10.1002/stem.1634.
    1. Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep. 2011;5:296. doi: 10.1186/1752-1947-5-296.
    1. Pak J, Chang JJ, Lee JH, Lee SH. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord. 2013;14:337. doi: 10.1186/1471-2474-14-337.
    1. Bui K, Duong T, Nguyen N, Nguyen T, Le V, Thanh Mai V, Lu-Chinh Phan N, Le Minh D, Ngoc N, Van Pham P. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomedical Research and Therapy. 2014;1:02–8. doi: 10.7603/s40730-014-0002-9.
    1. Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee. 2012;19:902–7. doi: 10.1016/j.knee.2012.04.001.
    1. Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi YJ. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy. 2013;29:748–55. doi: 10.1016/j.arthro.2012.11.017.
    1. Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2015;23:1308–16. doi: 10.1007/s00167-013-2807-2.
    1. Koh YG, Kwon OR, Kim YS, Choi YJ. Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy. 2014;30:1453–60. doi: 10.1016/j.arthro.2014.05.036.
    1. Michalek J, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, et al. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015.
    1. Kim YS, Park EH, Kim YC, Koh YG. Clinical outcomes of mesenchymal stem cell injection with arthroscopic treatment in older patients with osteochondral lesions of the talus. Am J Sports Med. 2013;41:1090–9. doi: 10.1177/0363546513479018.
    1. Kim YS, Lee HJ, Choi YJ, Kim YI, Koh YG. Does an injection of a stromal vascular fraction containing adipose-derived mesenchymal stem cells influence the outcomes of marrow stimulation in osteochondral lesions of the talus? A clinical and magnetic resonance imaging study. Am J Sports Med. 2014;42:2424–34. doi: 10.1177/0363546514541778.
    1. Koh YG, Choi YJ, Kwon OR, Kim YS. Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med. 2014;42:1628–37. doi: 10.1177/0363546514529641.
    1. Kim YS, Choi YJ, Suh DS, Heo DB, Kim YI, Ryu JS, Koh YG. Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold? Am J Sports Med. 2015;43:176–85. doi: 10.1177/0363546514554190.
    1. Kim YS, Choi YJ, Lee SW, Kwon OR, Suh DS, Heo DB, Koh YG. Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthritis Cartilage. 2016;24:237–45. doi: 10.1016/j.joca.2015.08.009.
    1. Kim YS, Choi YJ, Koh YG. Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes. Am J Sports Med. 2015;43:2293–301. doi: 10.1177/0363546515588317.
    1. Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH. Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial. Arthroscopy. 2016;32:97–109. doi: 10.1016/j.arthro.2015.09.010.
    1. Kim YS, Kwon OR, Choi YJ, Suh DS, Heo DB, Koh YG. Comparative matched-pair analysis of the injection versus implantation of mesenchymal stem cells for knee osteoarthritis. Am J Sports Med. 2015;43:2738–46. doi: 10.1177/0363546515599632.
    1. Sekiya I, Muneta T, Horie M, Koga H. Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects. Clin Orthop Relat Res. 2015;473:2316–26. doi: 10.1007/s11999-015-4324-8.
    1. Skowronski J, Rutka M. Osteochondral lesions of the knee reconstructed with mesenchymal stem cells—results. Ortop Traumatol Rehabil. 2013;15:195–204. doi: 10.5604/15093492.1058409.

Source: PubMed

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