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

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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 16 Bongso A, Lee EH. Stem Cells: From Bench to Bedside. Singapore: World Scientific Publishing Co. Pte. Ltd; 2011
• 17 Caplan AI. New era of cell-based orthopedic therapies. Tissue Eng Part B Rev 2009; 15 (2) 195-200
• 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
• 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
• 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
• 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
• 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
• 23 42 U.S.C. § 262 (i)(1)
• 24 21 U.S.C. § 321(g)(1)(B)-(C)
• 25 21 U.S.C. § 360(c)
• 26 21 CFR. 1271
• 27 21 CFR. 1271.3
• 28 21 CFR. 1271.15(b)
• 29 21 CFR. 1271.10
• 30 21 CFR 1271.3(b) and (e), respectively
• 31 21 CFR. 1271.(1)
• 32 32 CFR. 1271.440
• 33 US v. Regenerative Sciences, LLC, 741 F.3d 1314 (D.C. Cir. 2014)
• 34 21 C.F.R. 201.5
• 35 FDA Minimal Manipulation of Human Cells, Tissues and Cellular and Tissue-Based Products; December 2014
• 36 FDA Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations; December 2014
• 37 FDA Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; October 2014
• 38 Declaration of Steven R. Bauer, PhD, US v. Regenerative Sciences, LLC. (D.D.C. January 7, 2011)