Advertisement

Stem Cell Therapies for Post-Traumatic Arthritis

  • Farshid GuilakEmail author
  • Brian O. Diekman
  • Steven A. Olson
Chapter
  • 1k Downloads

Abstract

Post-traumatic arthritis is a progressive and debilitating joint disease that commonly occurs following joint trauma, such as ligament injury, meniscal tear, or intra-articular fracture. However, there are few therapeutic approaches currently available that have been shown to alter the course of this disease. Recent studies have shown that several different types of adult stem cells possess regenerative capabilities for a wide range of disease states. In particular, several studies have shown that exogenously delivered stem cells can enhance regeneration and diminish the severity or progression of post-traumatic arthritis. The mechanisms by which these cells act are not fully understood, but appear to involve the secretion of bioactive factors or the alteration of the cytokine and growth factor production of endogenous cells. Here we review the animal studies that have investigated the potential of stem cell therapies for reducing the severity of PTA, as well as some of the potential mechanisms that may be involved in these responses, and the current clinical trials being performed in this area.

Keywords

Mesenchymal stem cell Adipose stem cell Synovial stem cell Intra-articular therapy Immunomodulatory Cytokine Trophic 

Notes

Acknowledgments

Supported in part by the Arthritis Foundation, the Department of Defense, the Collaborative Research Center, AO Foundation, Davos Switzerland, and NIH grants AR48182, AR48852, AG15768, AR50245, and AG46927.

References

  1. 1.
    Anderson DD, Chubinskaya S, Guilak F, Martin JA, Oegema TR, Olson SA, Buckwalter JA. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. 2011;29(6):802–9.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20(10):739–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Frobell RB, Roos HP, Roos EM, Roemer FW, Ranstam J, Lohmander LS. Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial. BMJ. 2013;346:f232.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Marsh JL, Buckwalter J, Gelberman R, Dirschl D, Olson S, Brown T, Llinias A. Articular fractures: does an anatomic reduction really change the result? J Bone Joint Surg Am. 2002;84-A(7):1259–71.PubMedGoogle Scholar
  5. 5.
    Little CB, Hunter DJ. Post-traumatic osteoarthritis: from mouse models to clinical trials. Nat Rev Rheumatol. 2013;9(8):485–97.PubMedCrossRefGoogle Scholar
  6. 6.
    Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014;10(1):11–22.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Diekman BO, Guilak F. Stem cell-based therapies for osteoarthritis: challenges and opportunities. Curr Opin Rheumatol. 2013;25(1):119–26.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Iyer SS, Rojas M. Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies. Expert Opin Biol Ther. 2008;8(5):569–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views. Stem Cells. 2007;25(11):2896–902.PubMedCrossRefGoogle Scholar
  11. 11.
    Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012;20(1):14–20.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48(12):3464–74.PubMedCrossRefGoogle Scholar
  13. 13.
    Horie M, Sekiya I, Muneta T, Ichinose S, Matsumoto K, Saito H, Murakami T, Kobayashi E. Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells. 2009;27(4):878–87.PubMedCrossRefGoogle Scholar
  14. 14.
    Hatsushika D, Muneta T, Horie M, Koga H, Tsuji K, Sekiya I. Intraarticular injection of synovial stem cells promotes meniscal regeneration in a rabbit massive meniscal defect model. J Orthop Res. 2013;31(9):1354–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Hatsushika D, Muneta T, Nakamura T, Horie M, Koga H, Nakagawa Y, Tsuji K, Hishikawa S, Kobayashi E, Sekiya I. Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model. Osteoarthritis Cartilage. 2014;22(7):941–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol. 2012;47(6):458–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Toghraie FS, Chenari N, Gholipour MA, Faghih Z, Torabinejad S, Dehghani S, Ghaderi A. Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in rabbit. Knee. 2011;18(2):71–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Toghraie F, Razmkhah M, Gholipour MA, Faghih Z, Chenari N, Torabi Nezhad S, Nazhvani Dehghani S, Ghaderi A. Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med. 2012;15(8):495–9.PubMedGoogle Scholar
  19. 19.
    Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, Fini M, Giardino R, Facchini A, Grigolo B. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 2013;15(1):R22.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Singh A, Goel SC, Gupta KK, Kumar M, Arun GR, Patil H, Kumaraswamy V, Jha S. The role of stem cells in osteoarthritis: an experimental study in rabbits. Bone Joint Res. 2014;3(2):32–7.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Clark LD, Clark RK, Heber-Katz E. A new murine model for mammalian wound repair and regeneration. Clin Immunol Immunopathol. 1998;88(1):35–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Rai MF, Hashimoto S, Johnson EE, Janiszak KL, Fitzgerald J, Heber-Katz E, Cheverud JM, Sandell LJ. Heritability of articular cartilage regeneration and its association with ear wound healing in mice. Arthritis Rheum. 2012;64(7):2300–10.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Fitzgerald J, Rich C, Burkhardt D, Allen J, Herzka AS, Little CB. Evidence for articular cartilage regeneration in MRL/MpJ mice. Osteoarthritis Cartilage. 2008;16(11):1319–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Furman BD, Strand J, Hembree WC, Ward BD, Guilak F, Olson SA. Joint degeneration following closed intraarticular fracture in the mouse knee: a model of posttraumatic arthritis. J Orthop Res. 2007;25(5):578–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Ward BD, Furman BD, Huebner JL, Kraus VB, Guilak F, Olson SA. Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse. Arthritis Rheum. 2008;58(3):744–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Gourevitch D, Kossenkov AV, Zhang Y, Clark L, Chang C, Showe LC, Heber-Katz E. Inflammation and its correlates in regenerative wound healing: an alternate perspective. Adv Wound Care (New Rochelle). 2014;3(9):592–603.CrossRefGoogle Scholar
  27. 27.
    Lewis Jr JS, Furman BD, Zeitler E, Huebner JL, Kraus VB, Guilak F, Olson SA. Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL/MpJ mice. Arthritis Rheum. 2013;65(3):660–70.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Diekman BO, Wu CL, Louer CR, Furman BD, Huebner JL, Kraus VB, Olson SA, Guilak F. Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents posttraumatic arthritis. Cell Transplant. 2013;22(8):1395–408.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45:e54.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Pickvance EA, Oegema Jr TR, Thompson Jr RC. Immunolocalization of selected cytokines and proteases in canine articular cartilage after transarticular loading. J Orthop Res. 1993;11(3):313–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Irie K, Uchiyama E, Iwaso H. Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee. 2003;10(1):93–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology. 2002;39(1–2):237–46.PubMedGoogle Scholar
  33. 33.
    Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011;23(5):471–8.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Caron JP, Fernandes JC, Martel-Pelletier J, Tardif G, Mineau F, Geng C, Pelletier JP. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum. 1996;39(9):1535–44.PubMedCrossRefGoogle Scholar
  35. 35.
    Schulze-Tanzil G, Zreiqat H, Sabat R, Kohl B, Halder A, Muller RD, John T. Interleukin-10 and articular cartilage: experimental therapeutical approaches in cartilage disorders. Curr Gene Ther. 2009;9(4):306–15.PubMedCrossRefGoogle Scholar
  36. 36.
    Granero-Molto F, Weis JA, Miga MI, Landis B, Myers TJ, O’Rear L, Longobardi L, Jansen ED, Mortlock DP, Spagnoli A. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells. 2009;27(8):1887–98.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. 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(1):42–9.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Schelbergen RF, van Dalen S, ter Huurne M, Roth J, Vogl T, Noel D, Jorgensen C, van den Berg WB, van de Loo FA, Blom AB, van Lent PL. Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels. Osteoarthritis Cartilage. 2014;22(8):1158–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Park SA, Reilly CM, Wood JA, Chung DJ, Carrade DD, Deremer SL, Seraphin RL, Clark KC, Zwingenberger AL, Borjesson DL, Hayashi K, Russell P, Murphy CJ. Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland, the gland of the third eyelid and the knee joint. Cytotherapy. 2013;15(12):1498–510.PubMedCrossRefGoogle Scholar
  40. 40.
    Horie M, Choi H, Lee RH, Reger RL, Ylostalo J, Muneta T, Sekiya I, Prockop DJ. 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. Osteoarthritis Cartilage. 2012;20(10):1197–207.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Rodriguez-Merchan EC. Intra-articular injections of mesenchymal stem cells for knee osteoarthritis. Am J Orthop (Belle Mead NJ). 2014;43(12):E282–91.Google Scholar
  42. 42.
    Whitworth DJ, Banks TA. Stem cell therapies for treating osteoarthritis: prescient or premature? Vet J. 2014;202(3):416–24.PubMedCrossRefGoogle Scholar
  43. 43.
    Peeters CM, Leijs MJ, Reijman M, van Osch GJ, Bos PK. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage. 2013;21(10):1465–73.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Farshid Guilak
    • 1
    Email author
  • Brian O. Diekman
    • 2
  • Steven A. Olson
    • 3
  1. 1.Department of Orthopedic SurgeryDuke University Medical CenterDurhamUSA
  2. 2.Lineberger Comprehensive Cancer CenterUniversity of North Carolina, Chapel HillChapel HillUSA
  3. 3.Department of Orthopedic SurgeryDuke University Medical CenterDurhamUSA

Personalised recommendations