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Recent Clinical Trials in Adipose-derived Stem Cell Mediated Osteoarthritis Treatment

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  • Biomedical Engineering
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Abstract

Osteoarthritis (OA), a common chronic affliction amongst the elderly and athletes, is increasing every year. Due to the limited regenerative capacities of the cartilage, surgical or physical treatments have been developed for OA. The development of surgical treatment for OA has evolved from simple joint replacement to cell-based regeneration. Especially, compared with other types of stem cells, mesenchymal stem cells (bone-marrow derived stem cell (BMSC) and adipose-derived stem cell (ASC)) are well known for their high yield, excellent differentiation capacities and easy isolation, and hence are widely applied in tissue engineering. In addition, it has been known that a capability of chondrogenic differentiation of ASCs (i.e., mesenchymal stem cell population from a synovial origin) is higher than BMSCs. This review summarizes the recent clinical applications utilizing ASC and its clinical efficacy for OA treatment, estimated by applying available scoring systems. Current ASC therapy treatments in the clinical system include a direct injection of ASC supplemented with additional compounds such as platelet-rich plasma (PRP) and stromal vascular fraction (SVF) for enhancing differentiation of stem cells and the incorporation of ASC with biomaterial-based scaffolds such as fibrin and hyaluronic acid has been developed for more effective treatment than direct injection. Various scoring systems have demonstrated the clinical efficacy of ASC, and numerous results have validated the use of ASC as an OA therapy by relieving pain and improving the movement of cartilage. Furthermore, additional PRP or SVF combined with ASC have exhibited enhanced pain reduction and physiological movement of cartilage. Hence, clinical researches suggest that stem cell therapy utilizing ASC could be an effective OA treatment.

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Reference

  1. Chung, C. and J. A. Burdick (2008) Engineering cartilage tissue. Adv Drug Deliv. Rev. 60: 243–262.

    CAS  PubMed  Google Scholar 

  2. Chen, S. S., Y. H. Falcovitz, R. Schneiderman, A. Maroudas, and R. L. Sah (2001) Depth-dependent compressive properties of normal aged human femoral head articular cartilage: relationship to fixed charge density. Osteoarthritis Cartilage. 9: 561–569.

    CAS  PubMed  Google Scholar 

  3. Cho, H., D. Kim, and K. Kim (2018) Engineered co-culture strategies using stem cells for facilitated chondrogenic differentiation and cartilage repair. Biotechnol. Bioprocess Eng. 23: 261–270.

    CAS  Google Scholar 

  4. Davies-Tuck, M. L., A. E. Wluka, Y Wang, A. J. Teichtahl, G. Jones, C. Ding, and F. M. Cicuttini (2008) The natural history of cartilage defects in people with knee osteoarthritis. Osteoarthritis Cartilage. 16: 337–342.

    CAS  PubMed  Google Scholar 

  5. Cicuttini, F., C. Ding, A. Wluka, S. Davis, P. R. Ebeling, and G. Jones (2005) Association of cartilage defects with loss of knee cartilage in healthy, middle-age adults: a prospective study. Arthritis Rheum. 52: 2033–2039.

    PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  7. Arden, N. and M. C. Nevitt (2006) Osteoarthritis: epidemiology. Best Pract. Res. Clin. Rheumatol. 20: 3–25.

    PubMed  Google Scholar 

  8. Harrell, C. R., B. S. Markovic, C. Fellabaum, A. Arsenijevic, and V. Volarevic (2019) Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives. Biomed. Pharmacother. 109: 2318–2326.

    CAS  PubMed  Google Scholar 

  9. Schurman, D. J. and R. L. Smith (2004) Osteoarthritis: current treatment and future prospects for surgical, medical, and biologic intervention. Clin. Orthop. Relat. Res. 427: S183–S189.

    Google Scholar 

  10. Deyle, G. D., S. C. Allison, R. L. Matekel, M. G. Ryder, J. M. Stang, D. D. Gohdes, J. P. Hutton, N. E. Henderson, and M. B. Garber (2005) Physical therapy treatment effectiveness for osteoarthritis of the knee: a randomized comparison of supervised clinical exercise and manual therapy procedures versus a home exercise program. Phys. Ther. 85: 1301–1317.

    PubMed  Google Scholar 

  11. Kim, K., D. M. Yoon, A. G. Mikos, and F. K. Kasper (2012) Harnessing cell-biomaterial interactions for osteochondral tissue regeneration. Adv. Biochem. Eng. Biotechnol. 126: 67–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Memon, A. R. and J. F. Quinlan (2012) Surgical treatment of articular cartilage defects in the knee: are we winning? Adv. Orthop. 2012: 528423.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Gordey, E. E. and I. H. Wong (2018) Cartilage repair in the hip. Ann. Joint. 3: 24.

    Google Scholar 

  14. Bedi, A., B. T. Feeley, and R. J. Williams 3rd (2010) Management of articular cartilage defects of the knee. J. Bone Joint Surg. Am. 92: 994–1009.

    PubMed  Google Scholar 

  15. Bernardo, M. E., D. Pagliara, and F. Locatelli (2012) Mesenchymal stromal cell therapy: a revolution in regenerative medicine? Bone Marrow Transplant. 47: 164–171.

    CAS  PubMed  Google Scholar 

  16. Hwang, Y.-S., A. E. Bishop, J. M. Polak, and A. Mantalaris (2007) Enhanced in vitro chondrogenic differentiation of murine embryonic stem cells. Biotechnol. Bioprocess Eng. 12: 696–706.

    CAS  Google Scholar 

  17. Hwang, Y.-S., Y. Kang, and A. Mantalaris (2007) Directing embryonic stem cell differentiation into osteogenic chondrogenic lineage in vitro. Biotechnol. Bioprocess Eng. 12: 15–21.

    CAS  Google Scholar 

  18. Palumbo, P., F. Lombardi, G. Siragusa, M. G Cifone, B. Cinque, and M. Giuliani (2018) Methods of isolation, characterization and expansion of human adipose-derived stem cells (ascs): an overview. Int. J. Mol. Sci. 19: 1897.

    PubMed Central  Google Scholar 

  19. Zuk, P. A., M. Zhu, H. Mizuno, J. Huang, J. W. Futrell, A. J. Katz, P. Benhaim, H. P. Lorenz, and M. H. Hedrick (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7: 211–228.

    CAS  PubMed  Google Scholar 

  20. Van Pham, P., K. H. Bui, D. Q. Ngo, N. B. Vu, N. H. Truong, N. L. Phan, D. M. Le, T. D. Duong, T. D. Nguyen, V. T. Le, and N. K. Phan (2013) Activated platelet-rich plasma improves adiposederived stem cell transplantation efficiency in injured articular cartilage. Stem Cell Res. Ther. 4: 91.

    PubMed  PubMed Central  Google Scholar 

  21. Perdisa, F., N. Gostynska, A. Roffi, G. Filardo, M. Marcacci, and E. Kon (2015) Adipose-derived mesenchymal stem cells for the treatment of articular cartilage: a systematic review on preclinical and clinical evidence. Stem Cells Int. 2015: 597652.

    PubMed  PubMed Central  Google Scholar 

  22. Hached, F., C. Vinatier, C. Le Visage, H. Gonde, J. Guicheux, G. Grimandi, and A. Billon-Chabaud (2017) Biomaterial-assisted cell therapy in osteoarthritis: From mesenchymal stem cells to cell encapsulation. Best Pract. Res. Clin. Rheumatol. 31: 730–745.

    PubMed  Google Scholar 

  23. Pers, Y. M., M. Ruiz, D. Noel, and C. Jorgensen (2015) Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives. Osteoarthritis Cartilage. 23: 2027–2035.

    PubMed  Google Scholar 

  24. Mengshol, J. A., M. P. Vincenti, C. I. Coon, A. Barchowsky, and C. E. Brinckerhoff (2000) Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-jun N-terminal kinase, and nuclear factor kB: Differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum. 43: 801–811.

    CAS  PubMed  Google Scholar 

  25. Tetlow, L. C., D. J. Adlam, and D. E. Woolley (2001) Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: Associations with degenerative changes. Arthritis Rheum. 44: 585–594.

    CAS  PubMed  Google Scholar 

  26. Tofino-Vian, M., M. I. Guillen, M. D. Perez Del Caz, A. Silvestre, and M. J. Alcaraz (2018) Microvesicles from human adipose tissue-derived mesenchymal stem cells as a new protective strategy in osteoarthritic chondrocytes. Cell. Physiol. Biochem. 47: 11–25.

    CAS  PubMed  Google Scholar 

  27. Kim, Y. S., Y. J. Choi, D. S. Suh, D. B. Heo, Y. I. Kim, J. S. Ryu, and Y. G Koh (2015) Mesenchymal stem cell implantation in osteoarthritic knees is fibrin glue effective as a scaffold? Am. J. Sports Med. 43: 176–185.

    PubMed  Google Scholar 

  28. Kim, Y. S., Y. J. Choi, S. W. Lee, O. R. Kwon, D. S. Suh, D. B. Heo, and Y. G Koh (2016) Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthritis Cartilage. 24: 237–245.

    CAS  PubMed  Google Scholar 

  29. Kon, E., A. Roffi, G. Filardo, G. Tesei, and M. Marcacci (2015) Scaffold-based cartilage treatments: with or without cells? a systematic review of preclinical and clinical evidence. Arthroscopy. 31: 767–775.

    PubMed  Google Scholar 

  30. Koh, Y. G, Y. J. Choi, O. R. Kwon, and Y. S. Kim (2014) Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am. J. Sports Med. 42: 1628–1637.

    PubMed  Google Scholar 

  31. Spotnitz, W. D. (2014) Fibrin sealant: the only approved hemostat, sealant, and adhesive-a laboratory and clinical perspective. ISRNSurg. 2014: 203943.

    Google Scholar 

  32. Francis, S. L., S. Duchi, C. Onofrillo, C. Di Bella, and P. F. M. Choong (2018) Adipose-derived mesenchymal stem cells in the use of cartilage tissue engineering: the need for a rapid isolation procedure. Stem Cells Int. 2018: 8947548.

    PubMed  PubMed Central  Google Scholar 

  33. Robinson, P. G, I. R. Murray, C. C. West, E. B. Goudie, L. Y. Yong, T. O. White, and R. F. LaPrade (2018) Reporting of mesenchymal stem cell preparation protocols and composition: a systematic review of the clinical orthopaedic literature. Am. J. Sports Med. 47: 991–1000.

    PubMed  Google Scholar 

  34. Fellows, C. R., C. Matta, R. Zakany, I. M. Khan, and A. Mobasheri (2016) Adipose, bone marrow and synovial jointderived mesenchymal stem cells for cartilage repair. Front Genet. 7: 213.

    PubMed  PubMed Central  Google Scholar 

  35. Xie, X., Y. Wang, C. Zhao, S. Guo, S. Liu, W. Jia, R. S. Tuan, and C. Zhang (2012) Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials. 33: 7008–7018.

    CAS  PubMed  Google Scholar 

  36. Haefeli, M. and A. Elfering (2006) Pain assessment. Eur. Spine J. 15: S17–S24.

    PubMed  Google Scholar 

  37. Hawker, G. A., S. Mian, T. Kendzerska, and M. French (2011) Measures of adult pain: visual analog scale for pain (VAS pain), numeric rating scale for pain (NRS pain), McGill pain questionnaire (MPQ), short-form McGill pain questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res. (Hoboken). 63: S240–S252.

    Google Scholar 

  38. Ibrahim, T., A. Beiri, M. Azzabi, A. J. Best, G. J. Taylor, and D. K. Menon (2007) Reliability and validity of the subjective component of the American Orthopaedic Foot and Ankle Society clinical rating scales. J. Foot Ankle Surg. 46: 65–74.

    PubMed  Google Scholar 

  39. Madeley, N. J., K. J. Wing, C. Topliss, M. J. Penner, M. A. Glazebrook, and A. S. Younger (2012) Responsiveness and validity of the SF-36, ankle osteoarthritis scale, AOFAS ankle hindfoot score, and foot function index in end stage ankle arthritis. Foot Ankle Int. 33: 57–63.

    PubMed  Google Scholar 

  40. Pena, F., J. Agel, and J. C. Coetzee (2007) Comparison of the MFA to the AOFAS outcome tool in a population undergoing total ankle replacement. Foot Ankle Int. 28: 788–793.

    PubMed  Google Scholar 

  41. Van den Borne, M. P., N. J. Raijrnakers, J. Vanlauwe, J. Victor, S. N. de Jong, J. Bellernans, and D. B. Saris (2007) International cartilage repair society (ICRS) and oswestry macroscopic cartilage evaluation scores validated for use in autologous chondrocyte implantation (ACI) and microfracture. Osteoarthritis Cartilage. 15: 1397–1402.

    PubMed  Google Scholar 

  42. Bui, K.H.-T., T. D. Duong, N. T. Nguyen, T. D. Nguyen, V. T. Le, V. T. Mai, N. L.-C. Phan, D. M. Le, N. K. Phan, and P. Van Pham (2014) Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomed. Res. Ther. 1: 2–8.

    Google Scholar 

  43. Kellgren, J. H. and J. S. Lawrence (1957) Radiological assessment of osteo-arthrosis. Ann. Rheum. Dis. 16: 494–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Emrani, P. S., J. N. Katz, C. L. Kessler, W. M. Reichmann, E. A. Wright, T. E. McAlindon, and E. Losina (2008) Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis. Osteoarthritis Cartilage. 16: 873–882.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Roos, E. M., H. P. Roos, L. S. Lohmander, C. Ekdahl, and B. D. Beynnon (1998) knee injury and osteoarthritis outcome score (KOOS)—development of a self-administered outcome measure. J. Orthop. Sports Phys. Ther. 28: 88–96.

    CAS  PubMed  Google Scholar 

  46. Roos, E. M. and S. Toksvig-Larsen (2003) Knee injury and osteoarthritis outcome score (KOOS) — validation and comparison to the WOMAC in total knee replacement. Health Qual. Life Outcomes. 1: 17.

    PubMed  PubMed Central  Google Scholar 

  47. Collins, N. J., D. Misra, D. T. Felson, K. M. Crossley, and E. M. Roos (2011) Measures of knee function: International knee documentation committee (IKDC) subjective knee evaluation form, knee injury and osteoarthritis outcome score (KOOS), knee injury and osteoarthritis outcome score physical function short form (KOOS-PS), knee outcome survey activities of daily living scale (KOS-ADL), lysholm knee scoring scale, oxford knee score (OKS), western ontario and mcmaster universities osteoarthritis index (WOMAC), activity rating scale (ARS), and tegner activity score (TAS). Arthritis Care Res. (Hoboken). 63: S208–S228.

    PubMed  PubMed Central  Google Scholar 

  48. Gandek, B. (2015) Measurement properties of the Western Ontario and McMaster Universities Osteoarthritis Index: a systematic review. Arthritis Care Res. (Hoboken). 67: 216–229.

    PubMed  Google Scholar 

  49. Faschingbauer, M., M. Kasparek, P. Schadler, A. Trubrich, S. Urlaub, and F. Boettner (2017) Predictive values of WOMAC, KOOS, and SF-12 score for knee arthroplasty: data from the OAI. Knee Surg. Sports Traumatol. Arthrosc. 25: 3333–3339.

    CAS  PubMed  Google Scholar 

  50. McConnell, S., P. Kolopack, and A. M. Davis (2001) The western ontario and mcmaster universities osteoarthritis index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum. 45: 453–461.

    CAS  PubMed  Google Scholar 

  51. Dougados, M. (2004) Monitoring osteoarthritis progression and therapy. Osteoarthritis Cartilage. 12: S55–S60.

    PubMed  Google Scholar 

  52. Higgins, L. D., M. K. Taylor, D. Park, N. Ghodadra, M. Marchant, R. Pietrobon, and C. Cook (2007) Reliability and validity of the international knee documentation committee (IKDC) Subjective Knee Form. Joint Bone Spine. 74: 594–599.

    PubMed  Google Scholar 

  53. Anderson, A. F., J. J. Irrgang, M. S. Kocher, B. J. Mann, and J. J. Harrast (2006) The international knee documentation committee subjective knee evaluation form: normative data. Am. J. Sports Med. 34: 128–135.

    PubMed  Google Scholar 

  54. Ebrahimzadeh, M. H., H. Makhmalbaf, F. Golhasani-Keshtan, S. Rabani, and A. Birjandinejad (2015) The international knee documentation committee (IKDC) subjective short form: a validity and reliability study. Knee Surg. Sports Traumatol. Arthrosc. 23: 3163–3167.

    PubMed  Google Scholar 

  55. Briggs, K. K., M. S. Kocher, W. G. Rodkey, and J. R. Steadman (2006) Reliability, validity, and responsiveness of the Lysholm knee score and Tegner activity scale for patients with meniscal injury of the knee. J. Bone Joint Surg. Am. 88: 698–705.

    PubMed  Google Scholar 

  56. Hambly, K. (2011) The use of the Tegner Activity Scale for articular cartilage repair of the knee: a systematic review. Knee Surg. Sports Traumatol. Arthrosc. 19: 604–614.

    PubMed  Google Scholar 

  57. Fodor, P. B. and S. G. Paulseth (2016) Adipose derived stromal cell (ADSC) injections for pain management of osteoarthritis in the human knee joint. Aesthet Surg. J. 36: 229–236.

    PubMed  Google Scholar 

  58. Ronn, K., N. Reischl, E. Gautier, and M. Jacobi (2011) Current surgical treatment of knee osteoarthritis. Arthritis. 2011: 454873.

    PubMed  PubMed Central  Google Scholar 

  59. Kon, E., A. Gobbi, G. Filardo, M. Delcogliano, S. Zaffagnini, and M. Marcacci (2009) Arthroscopic second-generation autologous chondrocyte implantation compared with microfracture for chondral lesions of the knee: prospective nonrandomized study at 5 years. Am. J. Sports Med. 37: 33–41.

    PubMed  Google Scholar 

  60. Spakova, T., J. Rosocha, M. Lacko, D. Harvanova, and A. Gharaibeh (2012) Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am. J. Phys. Med. Rehabil. 91: 411–417.

    PubMed  Google Scholar 

  61. Ayhan, E., H. Kesmezacar, and I. Akgun (2014) Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. World J. Orthop. 5: 351–361.

    PubMed  PubMed Central  Google Scholar 

  62. Burke, J., M. Hunter, R. Kolhe, C. Isales, M. Hamrick, and S. Fulzele (2016) Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clin. Transl. Med. 5: 27.

    PubMed  PubMed Central  Google Scholar 

  63. Bansal, H., K. Comella, J. Leon, P. Verma, D. Agrawal, P. Koka, and T. Ichim (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: 141.

    PubMed  PubMed Central  Google Scholar 

  64. Hudetz, D., I. Boric, E. Rod, Z. Jelec, A. Radic, T. Vrdoljak, A. Skelin, G. Lauc, I. Trbojevic-Akmacic, M. Plecko, O. Polasek, and D. Primorac (2017) The effect of intra-articular injection of autologous microfragmented fat tissue on proteoglycan synthesis in patients with knee osteoarthritis. Genes (Basel). 8: 270.

    PubMed Central  Google Scholar 

  65. Jo, C. H., Y. G. Lee, W. H. Shin, H. Kim, J. W. Chai, E. C. Jeong, J. E. Kim, H. Shim, J. S. Shin, I. S. Shin, J. C. Ra, S. Oh, and K. S. Yoon (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: 1254–1266.

    CAS  PubMed  Google Scholar 

  66. Jo, C. H., J. W. Chai, E. C. Jeong, S. Oh, J. S. Shin, H. Shim, and K. S. Yoon (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: 2774–2783.

    PubMed  Google Scholar 

  67. Orozco, L., A. Munar, R. Soler, M. Alberca, F. Soler, M. Huguet, J. Sentis, A. Sanchez, and J. Garcia-Sancho (2013) Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 95: 1535–1541.

    CAS  PubMed  Google Scholar 

  68. Sekiya, I., T. Muneta, M. Horie, and H. Koga (2015) Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects. Clin. Orthop. Relat. Res. 473: 2316–2326.

    PubMed  PubMed Central  Google Scholar 

  69. Pers, Y. M., L. Rackwitz, R. Ferreira, O. Pullig, C. Delfour, F. Barry, L. Sensebe, L. Casteilla, S. Fleury, P. Bourin, D. Noel, F. Canovas, C. Cyteval, G. Lisignoli, J. Schrauth, D. Haddad, S. Domergue, U. Noeth, C. Jorgensen, and A. Consortium (2016) Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase i dose-escalation trial. Stem Cells Transl. Med. 5: 847–856.

    PubMed  PubMed Central  Google Scholar 

  70. Koh, Y. G. and Y. J. Choi (2012) Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee. 19: 902–907.

    PubMed  Google Scholar 

  71. Koh, Y. G, Y. J. Choi, S. K. Kwon, Y. S. Kim, and J. E. Yeo (2015) Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc. 23: 1308–1316.

    PubMed  Google Scholar 

  72. Kim, Y. S. and Y. G. Koh (2016) Injection of mesenchymal stem cells as a supplementary strategy of marrow stimulation improves cartilage regeneration after lateral sliding calcaneal osteotomy for varus ankle osteoarthritis: clinical and second-look arthroscopic results. Arthroscopy. 32: 878–889.

    PubMed  Google Scholar 

  73. Kim, Y. S., H. J. Lee, Y. J. Choi, Y. I. Kim, and Y. G Koh (2014) 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. 42: 2424–2434.

    PubMed  Google Scholar 

  74. Kim, Y. S., E. H. Park, Y. C. Kim, and Y. G. Koh (2013) Clinical outcomes of mesenchymal stem cell injection with arthroscopic treatment in older patients with osteochondral lesions of the talus. Am. J. Sports Med. 41: 1090–1099.

    Google Scholar 

  75. Hangody, L., G. Kish, L. Modis, I. Szerb, L. Gaspar, Z. Dioszegi, and Z. Kendik (2001) Mosaicplasty for the treatment of osteochondritis dissecans of the talus: two to seven year results in 36 patients. Foot Ankle Int. 22: 552–558.

    CAS  PubMed  Google Scholar 

  76. van Buul, G. M., W. L. Koevoet, N. Kops, P. K. Bos, J. A. Verhaar, H. Weinans, M. R. Bernsen, and G. J. van Osch (2011) Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am. J. Sports Med. 39: 2362–2370.

    PubMed  Google Scholar 

  77. Kuroda, K., T. Kabata, K. Hayashi, T. Maeda, Y. Kajino, S. Iwai, K. Fujita, K. Hasegawa, D. Inoue, N. Sugimoto, and H. Tsuchiya (2015) The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression. BMC Musculoskelet Disord. 16: 236.

    PubMed  PubMed Central  Google Scholar 

  78. Veronesi, F., M. Maglio, M. Tschon, N. N. Aldini, and M. Fini (2014) Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies. J. Biomed. Mater. Res. A. 102: 2448–2466.

    PubMed  Google Scholar 

  79. Kim, Y. S., Y. J. Choi, and Y. G. Koh (2015) Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes. Am. J. Sports Med. 43: 2293–2301.

    PubMed  Google Scholar 

  80. Park, E. H., H. S. Lim, S. Lee, K. Roh, K. W. Seo, K. S. Kang, and K. Shin (2018) Intravenous infusion of umbilical cord bloodderived mesenchymal stem cells in rheumatoid arthritis: a phase la clinical trial. Stem Cells Transl. Med. 7: 636–642.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Alvaro-Gracia, J. M., J. A. Jover, R. Garcia-Vicuna, L. Carreno, A. Alonso, S. Marsal, F. Blanco, V. M. Martinez-Taboada, P. Taylor, C. Martin-Martin, O. DelaRosa, I. Tagarro, and F. Diaz-Gonzalez (2017) Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann. Rheum. Dis. 76: 196–202.

    CAS  PubMed  Google Scholar 

  82. Pak, J. (2011) 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. 5: 296.

    PubMed  PubMed Central  Google Scholar 

  83. Pak, J., J. J. Chang, J. H. Lee, and S. H. Lee (2013) Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord. 14: 337.

    PubMed  PubMed Central  Google Scholar 

  84. Pak, J., J. H. Lee, K. S. Park, B. C. Jeong, and S. H. Lee (2016) Regeneration of cartilage in human knee osteoarthritis with autologous adipose tissue-derived stem cells and autologous extracellular matrix. Biores Open Access. 5: 192–200.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgement

This research work was supported by NRF grant funded by the Korea government (MSIP) (NRF-2017R1C1B1003665).

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Cho, H., Kim, H., Kim, Y.G. et al. Recent Clinical Trials in Adipose-derived Stem Cell Mediated Osteoarthritis Treatment. Biotechnol Bioproc E 24, 839–853 (2019). https://doi.org/10.1007/s12257-019-0255-7

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