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Perspective on Intra-articular Injection Cell Therapy for Osteoarthritis Treatment

  • Review Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Osteoarthritis (OA), the most common arthritis, is one of the most frequently encountered orthopaedic conditions. As a small number of large joints such as knee and hip are affected in OA, OA is an ideal target for local therapy. Although corticosteroid and hyaluronic acid have been traditionally used for joints through intra-articular (IA) injection, IA injection also provides a minimally invasive route to apply cell therapy to treat OA. IA cell therapy has drawn attention because it may provide regeneration of articular cartilage in addition to palliative anti-inflammatory effects.

Methods:

Current progress of IA injection therapy and the author’s perspective on this issue are described narratively.

Results:

It is too premature to have any conclusion on the eventual efficacy of IA cell therapy concerning regeneration of articular cartilage based on current data. Prospective radiological and histological data from larger numbers of patients are needed to prove cost effectiveness of IA cell therapy.

Conclusions:

Expanding research in this field will produce further evidences to provide guidance on the eventual effectiveness of IA cell therapy in the future.

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Fig. 1

Reproduced with permission from Kang et al. [10]

Fig. 2

Reproduced with permission from Ko et al. [21]

Fig. 3
Fig. 4

Reproduced with permission from Ko et al. [32]

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References

  1. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7.

    Article  CAS  PubMed  Google Scholar 

  2. Im GI. Clinical use of stem cells in orthopaedics. Eur Cell Mater. 2017;33:183–96.

    Article  PubMed  Google Scholar 

  3. Caldwell JR. Intra-articular corticosteroids. Guide to selection and indications for use. Drugs. 1996;52:507–14.

    Article  CAS  PubMed  Google Scholar 

  4. Abramson S. Drug delivery in degenerative joint disease: where we are and where to go? Adv Drug Deliv Rev. 2006;58:125–7.

    Article  CAS  PubMed  Google Scholar 

  5. Neander G, Eriksson LO, Wållin-Boll E, Ersmark H, Grahnen A. Pharmacokinetics of intraarticular indomethacin in patients with osteoarthritis. Eur J Clin Pharmacol. 1992;42:301–5.

    Article  CAS  PubMed  Google Scholar 

  6. Gerwin N, Hops C, Lucke A. Intraarticular drug delivery in osteoarthritis. Adv Drug Deliv Rev. 2006;58:226–42.

    Article  CAS  PubMed  Google Scholar 

  7. Williams DF. The Williams dictionary of biomaterials. Liverpool: Liverpool University Press; 1999. p. 42.

    Google Scholar 

  8. Srinivasan PP, McCoy SY, Jha AK, Yang W, Jia X, Farach-Carson MC, et al. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis. Biomed Mater. 2012;7:024109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Johnson K, Zhu S, Tremblay MS, Payette JN, Wang J, Bouchez LC, et al. A stem cell-based approach to cartilage repair. Science. 2012;336:717–21.

    Article  CAS  PubMed  Google Scholar 

  10. Kang ML, Jeong SY, Im GI. Hyaluronic acid hydrogel functionalized with self-assembled micelles of amphiphilic pegylated kartogenin for the treatment of osteoarthritis. Tissue Eng Part A. 2017;23:630–9.

    Article  CAS  PubMed  Google Scholar 

  11. Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord. 2011;12:259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mak J, Jablonski C, Leonard CA, Dunn JF, Raharjo E, Matyas JR, et al. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci Rep. 2016;6:23076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012;64:3604–13.

    Article  CAS  PubMed  Google Scholar 

  14. von Bahr L, Batsis I, Moll G, Hägg M, Szakos A, Sundberg B, et al. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells. 2012;30:1575–8.

    Article  CAS  Google Scholar 

  15. Acharya C, Adesida A, Zajac P, Mumme M, Riesle J, Martin I, et al. Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation. J Cell Physiol. 2012;227:88–97.

    Article  CAS  PubMed  Google Scholar 

  16. Wu L, Prins HJ, Helder MN, van Blitterswijk CA, Karperien M. Trophic effects of mesenchymal stem cells in chondrocyte co-cultures are independent of culture conditions and cell sources. Tissue Eng Part A. 2012;18:1542–51.

    Article  CAS  PubMed  Google Scholar 

  17. Saulnier N, Viguier E, Perrier-Groult E, Chenu C, Pillet E, Roger T, et al. Intra-articular administration of xenogeneic neonatal mesenchymal stromal cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis. Osteoarthritis Cartilage. 2015;23:122–33.

    Article  CAS  PubMed  Google Scholar 

  18. Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 2013;15:R22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E 2–dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15:42–9.

    Article  CAS  PubMed  Google Scholar 

  20. Im GI. Tissue engineering in osteoarthritis: current status and prospect of mesenchymal stem cell therapy. BioDrugs. 2018;32:183–92.

    Article  PubMed  Google Scholar 

  21. Ko JY, Kim KI, Park S, Im GI. In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials. 2014;35:3571–81.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. Ko JY, Lee JS, Lee J, Im GI. Intra-articular xenotransplantation of adipose-derived stromal cells to treat osteoarthritis in a goat model. Tissue Eng Regen Med. 2017;14:65–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F. Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum. 2002;46:704–13.

    Article  PubMed  Google Scholar 

  25. Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15:422–8.

    PubMed  Google Scholar 

  26. Lopa S, Colombini A, Stanco D, de Girolamo L, Sansone V, Moretti M. Donor-matched mesenchymal stem cells from knee infrapatellar and subcutaneous adipose tissue of osteoarthritic donors display differential chondrogenic and osteogenic commitment. Eur Cell Mater. 2014;27:298–311.

    Article  CAS  PubMed  Google Scholar 

  27. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  CAS  PubMed  Google Scholar 

  28. Aust L, Devlin B, Foster SJ, Halvorsen YD, Hicok K, du Laney T, et al. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy. 2004;6:7–14.

    Article  CAS  PubMed  Google Scholar 

  29. Li CY, Wu XY, Tong JB, Yang XX, Zhao JL, Zheng QF, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther. 2015;6:55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, 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.

    Article  CAS  PubMed  Google Scholar 

  31. Afizah H, Hui JH. Mesenchymal stem cell therapy for osteoarthritis. J Clin Orthop Trauma. 2016;7:177–82.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ko JY, Lee J, Lee J, Ryu YH, Im GI. SOX-6, 9-transfected adipose stem cells to treat surgically-induced osteoarthritis in goats. Tissue Eng Part A. 2018. https://doi.org/10.1089/ten.TEA.2018.0189.

    Article  PubMed  Google Scholar 

  33. Soler R, Orozco L, Munar A, Huguet M, López R, Vives J, et al. Final results of a phase I-II trial using ex vivo expanded autologous mesenchymal stromal cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee. 2016;23:647–54.

    Article  PubMed  Google Scholar 

  34. 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.

    Article  PubMed  Google Scholar 

  35. Dashnyam K, Lee JH, Mandakhbayar N, Jin GZ, Lee HH, Kim HW. Intra-articular biomaterials-assisted delivery to treat temporomandibular joint disorders. J Tissue Eng. 2018. https://doi.org/10.1177/2041731418776514

    Article  PubMed  PubMed Central  Google Scholar 

  36. Piuzzi NS, Ng M, Chughtai M, Khlopas A, Ng K, Mont MA, et al. The stem-cell market for the treatment of knee osteoarthritis: a patient perspective. J Knee Surg. 2018;31:551–6.

    Article  PubMed  Google Scholar 

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Acknowledgement

This study was supported by a research Grant (2017M3A9B4064777) from the National Research Foundation of Korea.

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  1. Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang, 10326, Republic of Korea

    Gun-Il Im

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  1. Gun-Il Im
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Correspondence to Gun-Il Im.

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Im, GI. Perspective on Intra-articular Injection Cell Therapy for Osteoarthritis Treatment. Tissue Eng Regen Med 16, 357–363 (2019). https://doi.org/10.1007/s13770-018-00176-6

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  • DOI: https://doi.org/10.1007/s13770-018-00176-6

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