图书馆订阅: Guest
Begell Digital Portal Begell 数字图书馆 电子图书 期刊 参考文献及会议录 研究收集
器官移植长期效应期刊
SJR: 0.145 SNIP: 0.491 CiteScore™: 0.89

ISSN 打印: 1050-6934
ISSN 在线: 1940-4379

器官移植长期效应期刊

DOI: 10.1615/JLongTermEffMedImplants.2020035281
pages 31-47

Safety and Efficacy of Cultured/Noncultured Mesenchymal Stromal Cells without Concurrent Surgery for Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Michael Hall
University of California, Riverside School of Medicine, 92521 UCR Botanic Gardens Rd, Riverside, CA 92507
Joseph McCafferty
New York Medical College, School of Medicine, Valhalla, NY 10595
Avinesh Agarwalla
Department of Orthopaedic Surgery, Westchester Medical Center, Valhalla, NY 10595
Ikenna Nwachuku
University of Southern California, Department of Orthopedic Surgery, 2051 Marengo St., Boyle Heights, Los Angeles County, CA
Joseph N. Liu
Department of Orthopaedic Surgery, Loma Linda University Medical Center, Loma Linda, CA 92354
Nirav H. Amin
Restore Orthopedics, Orange, CA 92868

ABSTRACT

The quantity of studies investigating mesenchymal stromal cells (MSCs) for knee osteoarthritis (OA) treatment is not restricted, unlike the amount of randomized controlled trials (RCTs) that can be found in the literature. MSCs demonstrate a promising potential for safe pain relief of OA, yet indeterminate conclusions prevail due to heterogeneous reporting and study design. By evaluating PubMed and ScienceDirect for RCTs that describe patient-reported outcome measures (PROMs) and adverse events (AEs), we investigate safety and efficacy of MSCs for knee OA unaccompanied by adjuvant surgical intervention. This systematic review is performed in alignment with preferred reported items for systematic reviews and meta-analyses guidelines. In addition to PROMs and AEs, we review included studies for stromal cell variants, follow-up, and imaging modalities, reporting our results in tables and text. Twelve studies that ranged from 1 wk to 4 yr and examined 428 patients and 856 knees met inclusion criteria. Six studies (50%) evaluated bone marrow MSCs, five (42%) evaluated adipose-derived MSCs, and one (8%) evaluated umbilical cord MSCs. All studies reported significant PROM improvement. Mean improvements in the visual analog scale and Western Ontario and McMaster Universities Arthritis Index, ranging from 0 to 40 and 10 to 32 points, respectively, were observed. Of 343 total patients, 135 (39%) experienced AEs. Whereas most AEs involved self-limiting knee swelling and pain, only three (0.8%) were severe enough to require overnight hospitalization. MSCs without adjuvant surgery offer a safe and efficacious conservative treatment option in knee OA patients by alleviating and decreasing pain for up to 12 mo. However, study limitations and contradictory findings require more evidence regarding cartilage repair.

REFERENCES

  1. Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr J. Osteoarthritis. Lancet. 2015;386(9991):376-87. .

  2. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81(9):646-56. .

  3. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43(9):1905-15. .

  4. Vasiliadis HS, Wasiak J. Autologous chondrocyte im-plantation for full thickness articular cartilage defects of the knee. Cochrane Database Syst Rev. 2010 Oct 6;2010(10):CD003323. .

  5. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331(14):889-95. .

  6. 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(8):1717-29. .

  7. Caplan AI. New era of cell-based orthopedic therapies. Tissue Eng B Rev. 2009;15(2):195-200. .

  8. Alhadlaq A, Mao JJ. Mesenchymal stem cells: Isolation and therapeutics. Stem Cells Dev. 2004;13(4):436-48. .

  9. 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;9859:1-13. .

  10. Filardo G, Perdisa F, Roffi A, Marcacci M, Kon E. Stem cells in articular cartilage regeneration. J Orthop Surg Res. 2016;11:42. .

  11. Emadedin M, Labibzadeh N, Liastani MG, Karimi A, Jaroughi N, Bolurieh T, Housenni T, Baharvan H, Aghmadi N. 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. 2018;20(10):1238-46. .

  12. Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O'Connor MI. A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis. Am J Sports Med. 2017;45(1):82-90. .

  13. Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Lopez-Elio S, Andreu E, Sanchez-Guijo F, Aquerreta JD, Bondia JM, Valenti-Azcarate A, Del Consuelo Del Canizo M, Villaron EM, Valenti-Nin JR, Prosper F. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: Long-term follow up of a multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2018;16(1):213. .

  14. Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Lopez-Elio S, Andreu E, Sanchez-Guijo F, Aquerreta JD, Bondia JM, Valenti-Azcarate A, Del Consuelo Del Canizo M, Villaron EM, Valenti-Nin JR, Prosper F. 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. 2016;14(1):246. .

  15. Vega A, Martln-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes J, Huguet M, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: A randomized controlled trial. Transplantation. 2015;99(8):1681-90. .

  16. Gupta PK, Chullikana A, Rengasamy M, Shetty N, Pandey V, Agarwal V. Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (StempeucelR): Preclinical and clinical trial in osteoarthritis of the knee joint. Arthrit Res Ther. 2016 Dec 20;18(1):301. .

  17. Lee W-S, Kim HJ, Kim K-I, Kim GB, Jin W. Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: A phase IIb, randomized, placebo-controlled clinical trial. Stem Cells Trans Med. 2019;8(6):504-11. .

  18. 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. 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. 2019;10(1):143. .

  19. Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, Paderson K, Boyd R. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteo-arthritis: A randomized controlled trial. Regenerat Med. 2019;14(3):213-30. .

  20. Jones IA, Wilson M, Togashi R, Han B, Mircheff AK, Thomas Vangsness C Jr. 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 Musculoskel Disorders. 2018;19(1):383. .

  21. Hong Z, Chen J, Zhang S, Zhao C, Bi M, Chen X, Bi Q. Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: A double-blind randomized self-controlled trial. Int Ortho. 2019;43(5):1123-34. .

  22. Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, Alcayaga-Miranda F, Gonzalez PL, Mus E, Khoury M, Figueroa FE, Espinoza F. 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 Trans Med. 2019;8(3):215-24. .

  23. Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH. Stem cell injections in knee osteoarthritis: A systematic review of the literature. Br J Sports Med. 2017;51(15):1125-33. .

  24. Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthrit Res Ther. 2008;10(5):223. .

  25. Koga H, Muneta T, Nagase T, Nimura A, Ju YJ, Mochizuki T, Sekayi Y. 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(2):207-15. .

  26. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294-301. .

  27. Ha CW, Park YB, Kim SH, Lee HJ. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: A systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy. 2019;35(1):277-88.e2. .

  28. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33-42. .

  29. Roman-Blas JA, Stokes DG, Jimenez SA. Modulation of TGF-P signaling by proinflammatory cytokines in articular chondrocytes. Osteoarthritis Cartilage. 2007;15(12):1367-77. .

  30. Kondo M, Yamaoka K, Sonomoto K, Fukuyo S, Oshita K, Okada Y, Tanka Y. IL-17 Inhibits chondrogenic differ-entiation of human mesenchymal stem cells. PLoS One. 2013;8(11):e79463. .

  31. Vaca-Gonzalez JJ, Guevara JM, Moncayo MA, Castro-Abril H, Hata Y, Garzon-Alvarado DA. Biophysical stimuli: A review of electrical and mechanical stimulation in hyaline cartilage. Cartilage. 2019;10(2):157-72. .

  32. Zhou Y, Tsai TL, Li WJ. Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo. Ann NY Acad Sci. 2017;1409(1):3-17. .

  33. Waldman SD, Couto DC, Grynpas MD, Pilliar RM, Kandel RA. Multi-axial mechanical stimulation of tissue engineered cartilage: Review. Eur Cell Mater. 2007;13:66-73. .

  34. Li Z, Kupcsik L, Yao SJ, Alini M, Stoddart MJ. Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-P pathway. J Cell Mol Med. 2010;14(6a):1338-46. .

  35. Saleh FA, Frith JE, Lee JA, Genever PG. Three-dimensional in vitro culture techniques for mesenchymal stem cells. Methods Mol Biol. 2012;916:31-45. .

  36. Yang Y, Lin H, Shen H, Wang B, Lei G, Tuan RS. Mesenchymal stem cell-derived extracellular matrix enhances chondrogenic phenotype of and cartilage formation by encapsulated chondrocytes in vitro and in vivo. Acta Biomater. 2018;69:71-82. .

  37. Izadifar Z, Chen X, Kulyk W. Strategic design and fabrication of engineered scaffolds for articular cartilage repair. J Funct Biomater. 2012;3(4):799-838. .

  38. Han S, Zhao Y, Xiao Z, Han J, Chen B, Chen L, Dai J. The three-dimensional collagen scaffold improves the stemness of rat bone marrow mesenchymal stem cells. J Genet Genom. 2012;39(12):633-41. .

  39. Kanichai M, Ferguson D, Prendergast PJ, Campbell VA. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: A role for AKT and hypoxia-inducible factor (HIF)-1a. J Cell Physiol. 2008;216(3):708-15. .

  40. Tsai TL, Manner PA, Li WJ. Regulation of mesenchymal stem cell chondrogenesis by glucose through protein kinase C/transforming growth factor signaling. Osteoarthritis Cartilage. 2013;21(2):368-76. .


Articles with similar content:

Systematic Review of Single-Set Versus Multiple-Set Resistance-Training Randomized Controlled Trials: Implications for Rehabilitation
Critical Reviews™ in Physical and Rehabilitation Medicine, Vol.18, 2006, issue 2
Daniel Hermsen, Christopher Demuth, Christopher J. Durall
Review of Lower Extremity Function Following SEMLS in Children with Cerebral Palsy
Critical Reviews™ in Physical and Rehabilitation Medicine, Vol.31, 2019, issue 2
Ashok Johari, Sailaxmi Ganesan, Triveni Shetty, Rajani Mullerpatan
Effectiveness of Negative-Pressure Wound Therapy following Total Hip and Knee Replacements
Journal of Long-Term Effects of Medical Implants, Vol.29, 2019, issue 1
Videshnandan Raut, Hosam E. Matar, Nicholas Emms
Use of Combined Magnetic Field Treatment for Fracture Nonunion
Journal of Long-Term Effects of Medical Implants, Vol.26, 2016, issue 3
Jon Zoltan, Sheila Sprague, Mark Phillips, Judy Baumhauer
Excellent Early Outcomes of the First 100 Cruciate-Retaining TriathlonTM Total Knee Arthroplasties
Journal of Long-Term Effects of Medical Implants, Vol.23, 2013, issue 1
Robert Pivec, Mark J. McElroy, Swetha Dhanireddy, Michael A. Mont, Qais Naziri, Kimona Issa, Aaron J. Johnson