Regenerative Rehabilitative Medicine for Joints and Muscles


Purpose of Review

The purpose of this paper was to review regenerative medicine treatments for joints and muscles.

Recent Findings

There is level 1 evidence supporting the use of platelet-rich plasma (PRP) injections for the treatment of osteoarthritis (OA). Few studies have investigated the efficacy and safety of bone marrow aspirate concentrate (BMAC), microfragmented fat (MF), and placental and amniotic product (PAP) injections for OA. Preliminary studies have not found a benefit of PRP injections for acute muscle injury. No studies have been performed evaluating the therapeutic effect of BMAC, MF, or PAP injections for muscle injuries.


Based upon the currently available research, PRP injections for OA provide more significant pain relief and functional improvement than placebo or hyaluronic acid and are more effective in the knee than in the hip. There is insufficient evidence to determine whether BMAC, MF, or PAP injections are safe or efficacious for the treatment of OA or whether any regenerative medicine injection is safe or effective for muscle injuries.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    National Institutes of Health Fact sheets: regenerative medicine. In: Services USDoHaH, editor. Online 2010.

  2. 2.

    Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol. 2012;13(7):1185–95.

  3. 3.

    • Mautner K, Malanga GA, Smith J, Shiple B, Ibrahim V, Sampson S, et al. A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature. PM R. 2015;7(4 Suppl):S53–S9. article provides a description of a recommended PRP classification system that is commonly being used in research studies.

  4. 4.

    DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Arthroscopy. 2012;28(7):998–1009.

  5. 5.

    Dohan Ehrenfest DM, Bielecki T, Mishra A, Borzini P, Inchingolo F, Sammartino G, et al. In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes. Curr Pharm Biotechnol. 2012;13(7):1131–7.

  6. 6.

    Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol. 2009;27(3):158–67.

  7. 7.

    Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg. 1993;165(6):728–37.

  8. 8.

    Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med. 2009;37(11):2259–72.

  9. 9.

    Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med. 2009;28(1):113–25.

  10. 10.

    Piuzzi NS, Mantripragada VP, Sumski A, Selvam S, Boehm C, Muschler GF. Bone marrow-derived cellular therapies in orthopaedics: part I: recommendations for bone marrow aspiration technique and safety. JBJS Rev. 2018;6(11):e4.

  11. 11.

    Piuzzi NS, Mantripragada VP, Kwee E, Sumski A, Selvam S, Boehm C, et al. Bone marrow-derived cellular therapies in orthopaedics: part II: recommendations for reporting the quality of bone marrow-derived cell populations. JBJS Rev. 2018;6(11):e5.

  12. 12.

    • Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;6(6):1445–51. paper describes why it may be appropriate to change the name of mesenchymal stem cells to medicinal signaling cells.

  13. 13.

    Liao HT, Chen CT. Osteogenic potential: comparison between bone marrow and adipose-derived mesenchymal stem cells. World J Stem Cells. 2014;6(3):288–95.

  14. 14.

    Payne KA, Didiano DM, Chu CR. Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cells. Osteoarthr Cartil. 2010;18(5):705–13.

  15. 15.

    Jayaram P, Ikpeama U, Rothenberg JB, Malanga GA. Bone marrow-derived and adipose-derived mesenchymal stem cell therapy in primary knee osteoarthritis: a narrative review. PM R. 2019;11(2):177–91.

  16. 16.

    Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells. 2010;28(3):585–96.

  17. 17.

    Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–84.

  18. 18.

    Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45:e54.

  19. 19.

    Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008;129(3):163–73.

  20. 20.

    Tremolada C, Colombo V, Ventura C. Adipose tissue and mesenchymal stem cells: state of the art and Lipogems(R) technology development. Curr Stem Cell Rep. 2016;2:304–12.

  21. 21.

    Vezzani B, Shaw I, Lesme H, Yong L, Khan N, Tremolada C, et al. Higher pericyte content and secretory activity of microfragmented human adipose tissue compared to enzymatically derived stromal vascular fraction. Stem Cells Transl Med. 2018;7(12):876–86.

  22. 22.

    •• Malanga GA, Dona S, Borg-Stein J, Auriemma M, Singh JR. Refractory knee osteoarthritis: adipose-derived stromal cells versus bone marrow aspiration concentrate. PM R. 2018;10(5):524–32. study compares the efficacy of MF versus BMAC for the treatment of knee osteoarthritis.

  23. 23.

    Bain BJ. Morbidity associated with bone marrow aspiration and trephine biopsy—a review of UK data for 2004. Haematologica. 2006;91(9):1293–4.

  24. 24.

    Kaoutzanis C, Gupta V, Winocour J, Layliev J, Ramirez R, Grotting JC, et al. Cosmetic liposuction: preoperative risk factors, major complication rates, and safety of combined procedures. Aesthet Surg J. 2017;37(6):680–94.

  25. 25.

    Kim YH, Cha SM, Naidu S, Hwang WJ. Analysis of postoperative complications for superficial liposuction: a review of 2398 cases. Plast Reconstr Surg. 2011;127(2):863–71.

  26. 26.

    McIntyre JA, Jones IA, Danilkovich A, Vangsness CT Jr. The placenta: applications in orthopaedic sports medicine. Am J Sports Med. 2018;46(1):234–47.

  27. 27.

    • Riboh JC, Saltzman BM, Yanke AB, Cole BJ. Human amniotic membrane-derived products in sports medicine: basic science, early results, and potential clinical applications. Am J Sports Med. 2016;44(9):2425–34. article provides a nice review of PAP.

  28. 28.

    Koizumi NJ, Inatomi TJ, Sotozono CJ, Fullwood NJ, Quantock AJ, Kinoshita S. Growth factor mRNA and protein in preserved human amniotic membrane. Curr Eye Res. 2000;20(3):173–7.

  29. 29.

    Uchida S, Inanaga Y, Kobayashi M, Hurukawa S, Araie M, Sakuragawa N. Neurotrophic function of conditioned medium from human amniotic epithelial cells. J Neurosci Res. 2000;62(4):585–90.<585::AID-JNR13>3.0.CO;2-U.

  30. 30.

    Insausti CL, Blanquer M, Garcia-Hernandez AM, Castellanos G, Moraleda JM. Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application. Stem Cells Cloning. 2014;7:53–63.

  31. 31.

    Kjaergaard N, Hein M, Hyttel L, Helmig RB, Schonheyder HC, Uldbjerg N, et al. Antibacterial properties of human amnion and chorion in vitro. Eur J Obstet Gynecol Reprod Biol. 2001;94(2):224–9.

  32. 32.

    Niknejad H, Paeini-Vayghan G, Tehrani FA, Khayat-Khoei M, Peirovi H. Side dependent effects of the human amnion on angiogenesis. Placenta. 2013;34(4):340–5.

  33. 33.

    Mamede AC, Carvalho MJ, Abrantes AM, Laranjo M, Maia CJ, Botelho MF. Amniotic membrane: from structure and functions to clinical applications. Cell Tissue Res. 2012;349(2):447–58.

  34. 34.

    Panero AJ, Hirahara AM, Andersen WJ, Rothenberg J, Fierro F. Are amniotic fluid products stem cell therapies? A study of amniotic fluid preparations for mesenchymal stem cells with bone marrow comparison. Am J Sports Med. 2019;47(5):1230–5.

  35. 35.

    Berger D, Lyons N, Steinmetz N. In vitro evaluation of injectable, placental tissue-derived products for orthopedic applications. Interventional Orthopedics Foundation Conference; Broomfield, CO 2015.

  36. 36.

    •• Regulatory considerations for human cells, tissues, and cellular and tissue-based products: minimal manipulation and homologous use. Guidance for Industry and Food and Drug Administration staff. In: Services UDoHaH, Administration FaD, REsearch CfBEa, Health CfDaR, Products OoC, editors.2017. This guidance document from the FDA provides significant, relevant information related to the regulation of regenerative medicine products. Anyone interested in regenerative medicine shouled be familiar with the regulations surrounding their use.

  37. 37.

    Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26(3):355–69.

  38. 38.

    Sakellariou VI, Poultsides LA, Ma Y, Bae J, Liu S, Sculco TP. Risk assessment for chronic pain and patient satisfaction after total knee arthroplasty. Orthopedics. 2016;39(1):55–62.

  39. 39.

    Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS. Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014;95(3):562–75.

  40. 40.

    Laudy AB, Bakker EW, Rekers M, Moen MH. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49(10):657–72.

  41. 41.

    Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy. 2016;32(3):495–505.

  42. 42.

    Sadabad HN, Behzadifar M, Arasteh F, Behzadifar M, Dehghan HR. Efficacy of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: a systematic review and meta-analysis. Electron Physician. 2016;8(3):2115–22.

  43. 43.

    •• Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Arthroscopy. 2017;33(3):659–70 e1. recent meta-analysis provides the most up-to-date information regarding level 1 studies on PRP for knee OA.

  44. 44.

    Han Y, Huang H, Pan J, Lin J, Zeng L, Liang G, et al. Meta-analysis comparing platelet-rich plasma vs hyaluronic acid injection in patients with knee osteoarthritis. Pain Med. 2019.

  45. 45.

    Chung PY, Lin MT, Chang HP. Effectiveness of platelet-rich plasma injection in patients with temporomandibular joint osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(2):106–16.

  46. 46.

    Ye Y, Zhou X, Mao S, Zhang J, Lin B. Platelet rich plasma versus hyaluronic acid in patients with hip osteoarthritis: a meta-analysis of randomized controlled trials. Int J Surg. 2018;53:279–87.

  47. 47.

    Kim JD, Lee GW, Jung GH, Kim CK, Kim T, Park JH, et al. Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee. Eur J Orthop Surg Traumatol. 2014;24(8):1505–11.

  48. 48.

    •• 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. study compared the efficacy of BMAC injections versus placebo for knee osteoarthritis.

  49. 49.

    •• Shapiro SA, Arthurs JR, Heckman MG, Bestic JM, Kazmerchak SE, Diehl NN et al. Quantitative T2 MRI mapping and 12-month follow-up in a randomized, blinded, placebo controlled trial of bone marrow aspiration and concentration for osteoarthritis of the knees. Cartilage. 2018:1947603518796142. doi: This study compared the efficacy of BMAC injections versus placebo for knee osteoarthritis and evaluated whether there was any change in cartilage thickness 12 months after the injections between the two groups.

  50. 50.

    Centeno C, Sheinkop M, Dodson E, Stemper I, Williams C, Hyzy M, et al. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018;16(1):355.

  51. 51.

    Russo A, Condello V, Madonna V, Guerriero M, Zorzi C. Autologous and micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis. J Exp Orthop. 2017;4(1):33.

  52. 52.

    Russo A, Screpis D, Di Donato SL, Bonetti S, Piovan G, Zorzi C. Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: an update at 3 year follow-up. J Exp Orthop. 2018;5(1):52–5.

  53. 53.

    Panchal J, Malanga G, Sheinkop M. Safety and efficacy of percutaneous injection of Lipogems micro-fractured adipose tissue for osteoarthritic knees. Am J Orthop (Belle Mead NJ). 2018;47(11). doi:

  54. 54.

    Dall’Oca C, Breda S, Elena N, Valentini R, Samaila EM, Magnan B. Mesenchymal stem cells injection in hip osteoarthritis: preliminary results. Acta Biomed. 2019;90(1-S):75–80.

  55. 55.

    Schiavone Panni A, Vasso M, Braile A, Toro G, De Cicco A, Viggiano D, et al. Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response. Int Orthop. 2019;43(1):7–13.

  56. 56.

    • Gellhorn AC, Han A. The use of dehydrated human amnion/chorion membrane allograft injection for the treatment of tendinopathy or arthritis: a case series involving 40 patients. PM R. 2017;9(12):1236–43. this is a case series, it is the study with the highest level of evidence for treating osteoarthritis with PAP.

  57. 57.

    Ekstrand J, Hagglund M, Walden M. Epidemiology of muscle injuries in professional football (soccer). Am J Sports Med. 2011;39(6):1226–32.

  58. 58.

    •• Grassi A, Napoli F, Romandini I, Samuelsson K, Zaffagnini S, Candrian C, et al. Is platelet-rich plasma (PRP) effective in the treatment of acute muscle injuries? A systematic review and meta-analysis. Sports Med. 2018;48(4):971–89. is a recent meta-analysis evaluating the efficacy of PRP in muscle injuries.

  59. 59.

    •• Setayesh K, Villarreal A, Gottschalk A, Tokish JM, Choate WS. Treatment of muscle injuries with platelet-rich plasma: a review of the literature. Curr Rev Musculoskelet Med. 2018;11(4):635–42. is a recent meta-analysis evaluating the efficacy of PRP in muscle injuries.

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Correspondence to Jonathan T. Finnoff.

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Jonathan Finnoff reports being a medical advisory board member for COVR Medical, Sanofi, and Aim Specialty Health, and royalties from Demos Publishing and up-to-date outside the submitted work. Dr. Finnoff is also a member of the AAPM&R board of governors.

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Finnoff, J.T. Regenerative Rehabilitative Medicine for Joints and Muscles. Curr Phys Med Rehabil Rep (2020).

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  • Regenerative medicine
  • Platelet-rich plasma
  • Bone marrow
  • Mesenchymal stem cell