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J Knee Surg 2015; 28(01): 055-062
DOI: 10.1055/s-0034-1398470
Special Focus Section
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

FDA Regulation of Adult Stem Cell Therapies as Used in Sports Medicine

Mary Ann Chirba
1   Boston College Law School, Newton Centre, Massachusetts
,
Berkley Sweetapple
1   Boston College Law School, Newton Centre, Massachusetts
,
Charles P. Hannon
2   Georgetown University School of Medicine, Washington, District of Columbia
,
John A. Anderson
3   Department of Sports Medicine, Rothman Institute, Philadelphia, Pennsylvania
› Author Affiliations
Further Information

Publication History

21 May 2014

19 November 2014

Publication Date:
20 January 2015 (online)

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Abstract

In sports medicine, adult stem cells are the subject of great interest. Several uses of stem cells are under investigation including cartilage repair, meniscal regeneration, anterior cruciate ligament reconstruction, and tendinopathy. Extensive clinical and basic science research is warranted as stem cell therapies become increasingly common in clinical practice. In the United States, the Food and Drug Administration (FDA) is responsible for regulating the use of stem cells through its “Human Cells, Tissues, and Cellular and Tissue-Based Products” regulations. This report provides a brief overview of FDA regulation of adult stem cells. Several common clinical case scenarios are then presented that highlight how stem cells are currently being used in sports medicine and how current FDA regulations are likely to affect the physicians who use them. In the process, it explains how a variety of factors in sourcing and handling these cells, particularly the extent of cell manipulation, will affect what a physician can and cannot do without first obtaining the FDA's express approval.

Keywords

mesenchymal stem cells - adipose stem cells - HCT/Ps - FDA Section 361 - FDA Section 351 - minimal manipulation - sports medicine - cartilage - ACL - meniscus
 

  • References

  • 1 Koh YG, Choi YJ, Kwon OR, Kim YS. Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med 2014; 42 (7) 1628-1637
    CrossrefPubMedGoogle Scholar
  • 2 Jo CH, Lee YG, Shin WH , 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 (5) 1254-1266
    CrossrefPubMedGoogle Scholar
  • 3 Anderson JA, Little D, Toth AP , et al. Stem cell therapies for knee cartilage repair: the current status of preclinical and clinical studies. Am J Sports Med 2014; 42 (9) 2253-2261
    CrossrefPubMedGoogle Scholar
  • 4 Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med 2014; 42 (3) 648-657
    CrossrefPubMedGoogle Scholar
  • 5 Fan H, Liu H, Toh SL, Goh JCH. Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model. Biomaterials 2009; 30 (28) 4967-4977
    CrossrefPubMedGoogle Scholar
  • 6 Kanaya A, Deie M, Adachi N, Nishimori M, Yanada S, Ochi M. Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. Arthroscopy 2007; 23 (6) 610-617
    CrossrefPubMedGoogle Scholar
  • 7 Figueroa D, Espinosa M, Calvo R , et al. Anterior cruciate ligament regeneration using mesenchymal stem cells and collagen type I scaffold in a rabbit model. Knee Surg Sports Traumatol Arthrosc 2014; 22 (5) 1196-1202
    CrossrefPubMedGoogle Scholar
  • 8 Proffen BL, Haslauer CM, Harris CE, Murray MM. Mesenchymal stem cells from the retropatellar fat pad and peripheral blood stimulate ACL fibroblast migration, proliferation, and collagen gene expression. Connect Tissue Res 2013; 54 (1) 14-21
    CrossrefPubMedGoogle Scholar
  • 9 Beitzel K, Solovyova O, Cote MP , et al. The future role of mesenchymal stem cells in the management of shoulder disorders. Arthroscopy 2013; 29 (10) 1702-1711
    CrossrefPubMedGoogle Scholar
  • 10 Ruzzini L, Longo UG, Rizzello G, Denaro V. Stem cells and tendinopathy: state of the art from the basic science to clinic application. Muscles Ligaments Tendons J 2012; 2 (3) 235-238
    PubMedGoogle Scholar
  • 11 Pascual-Garrido C, Rolón A, Makino A. Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int 2012; 2012: 953510
    PubMedGoogle Scholar
  • 12 Isaac C, Gharaibeh B, Witt M, Wright VJ, Huard J. Biologic approaches to enhance rotator cuff healing after injury. J Shoulder Elbow Surg 2012; 21 (2) 181-190
    CrossrefPubMedGoogle Scholar
  • 13 Zellner J, Hierl K, Mueller M , et al. Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone. J Biomed Mater Res B Appl Biomater 2013; 101 (7) 1133-1142
    CrossrefPubMedGoogle Scholar
  • 14 Hatsushika D, Muneta T, Nakamura T , et al. Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model. Osteoarthritis Cartilage 2014; 22 (7) 941-950
    CrossrefPubMedGoogle Scholar
  • 15 Vangsness Jr CTJ, Farr II J, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am 2014; 96 (2) 90-98
    CrossrefPubMedGoogle Scholar
  • 16 Bongso A, Lee EH. Stem Cells: From Bench to Bedside. Singapore: World Scientific Publishing Co. Pte. Ltd; 2011
    CrossrefGoogle Scholar
  • 17 Caplan AI. New era of cell-based orthopedic therapies. Tissue Eng Part B Rev 2009; 15 (2) 195-200
    CrossrefPubMedGoogle Scholar
  • 18 Murray IR, Corselli M, Petrigliano FA, Soo C, Péault B. Recent insights into the identity of mesenchymal stem cells: Implications for orthopaedic applications. Bone Joint J 2014; 96-B (3) 291-298
    CrossrefPubMedGoogle Scholar
  • 19 da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006; 119 (Pt 11) 2204-2213
    Google Scholar
  • 20 Gimble JM, Guilak F, Bunnell BA. Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther 2010; 1 (2) 19
    CrossrefPubMedGoogle Scholar
  • 21 Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM. 2010 Nicolas Andry Award: Multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering. Clin Orthop Relat Res 2010; 468 (9) 2530-2540
    CrossrefPubMedGoogle Scholar
  • 22 Koh YG, Jo S-B, Kwon OR , et al. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 2013; 29 (4) 748-755
    CrossrefPubMedGoogle Scholar
  • 23 42 U.S.C. § 262 (i)(1)
    PubMed
  • 24 21 U.S.C. § 321(g)(1)(B)-(C)
    PubMed
  • 25 21 U.S.C. § 360(c)
    PubMed
  • 26 21 CFR. 1271
    PubMed
  • 27 21 CFR. 1271.3
    PubMed
  • 28 21 CFR. 1271.15(b)
    PubMed
  • 29 21 CFR. 1271.10
    PubMed
  • 30 21 CFR 1271.3(b) and (e), respectively
    PubMed
  • 31 21 CFR. 1271.(1)
    PubMed
  • 32 32 CFR. 1271.440
    PubMed
  • 33 US v. Regenerative Sciences, LLC, 741 F.3d 1314 (D.C. Cir. 2014)
    PubMed
  • 34 21 C.F.R. 201.5
    PubMed
  • 35 FDA Minimal Manipulation of Human Cells, Tissues and Cellular and Tissue-Based Products; December 2014
    PubMed
  • 36 FDA Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations; December 2014
    PubMed
  • 37 FDA Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; October 2014
    PubMed
  • 38 Declaration of Steven R. Bauer, PhD, US v. Regenerative Sciences, LLC. (D.D.C. January 7, 2011)
    PubMed