The Journal of Contemporary Dental Practice

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 24 , ISSUE 2 ( February, 2023 ) > List of Articles


Japanese Laws and the Current Status of Regenerative Medicine in the Tohoku Region

Yuya Kamano, Noboru Terajima, Yuta Chiba, V Venkata Suresh, Masahiro Saito

Keywords : Japanese Laws on Regenerative Medicine, Regenerative medicine, Tohoku region

Citation Information : Kamano Y, Terajima N, Chiba Y, Suresh VV, Saito M. Japanese Laws and the Current Status of Regenerative Medicine in the Tohoku Region. J Contemp Dent Pract 2023; 24 (2):120-128.

DOI: 10.5005/jp-journals-10024-3487

License: CC BY-NC 4.0

Published Online: 23-05-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Aim: The aim of this study was to review Japanese laws regarding regenerative medicine and the current status of clinical application of regenerative medicine, to learn about the advantages and problems, and to thereby serve as a reference for measures necessary for the development of regenerative medicine. Background: Regenerative medicine started in 1957 with the transplantation of hematopoietic stem cells, followed by the establishment of embryonic stem cells in 1981 and induced pluripotent stem cells in 2006, and continues to evolve progressively. At the same time, however, problems have emerged due to lax legal regulations, such as the use of treatments that lack scientific evidence. Review results: The Japanese government enacted two laws to regulate regenerative medicine: the Law to Ensure the Safety of Regenerative Medicine and the Amend the Pharmaceutical Affairs Law in 2013. These laws were enacted with the aim of providing safe regenerative medicine promptly and smoothly and developing many regenerative medicine products. In these laws, regenerative medicine is defined as medical treatment that restores lost functions of damaged organs and tissues with the help of cellular and tissue-based products. Nowadays, there are two major methods of regenerative medicine. One representative method involves the transplantation of devices that activates self-regenerative ability by introducing living cells into patients’ body. The other method is the activation and differentiation of endogenous stem cells with cell growth and differentiation factors. Conclusion: The current status of regenerative medicine in the Tohoku region after the enactment of these laws is described in detail. This clarified the advantages and disadvantages associated with regenerative medicine as it is currently practiced in Japan. Clinical significance: Development of regenerative medicine in dentistry will be advanced by learning about its clinical application in medicine.

  1. Thomas ED, Lochte HL Jr, Lu WC, et al. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 1957;257(11):491–496. PMID: 13464965.
  2. Sawa Y, Miyagawa S. Cell sheet technology for heart failure. Curr pharm biotechnology. 2013;14(1):61–66. PMID: 23437937.
  3. Mandai M, Kurimoto Y, Takahashi M. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 2017;377(8):792–793. PMID: 28834478.
  4. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126(4):663–676. PMID: 16904174.
  5. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131(5):861–872. PMID: 18035408.
  6. Ikegami H, Noso S, Babaya N, et al. Genetics and pathogenesis of type 1 diabetes: Prospects for prevention and intervention. J Diabetes Invest 2011;2(6):415–420. PMID: 24843523.
  7. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000;343(4):230–238. PMID: 10911004.
  8. Yabe SG, Fukuda S, Nishida J, et al. Induction of functional islet-like cells from human iPS cells by suspension culture. Regener Ther 2019;10:69–76. PMID: 30623004.
  9. Kano M, Mizutani E, Homma S, et al. Xenotransplantation and interspecies organogenesis: Current status and issues. Front endocrinol 2022;13:963282. PMID: 35992127.
  10. Najarian JS, Sutherland DE, Matas AJ, et al. Human islet transplantation: A preliminary report. Transplant Proc 1977;9(1):233–236. PMID: 405770.
  11. Nagata H, Matsumoto S, Okitsu T, et al. In situ cooling of pancreata from non-heart-beating donors prior to procurement for islet transplantation. Transplant Proc. 2005;37(8):3393–3395. PMID: 16298604.
  12. Saito T, Gotoh M, Satomi S, et al. Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry. Transplantation 2010;90(7):740–747. PMID: 20811319.
  13. Alves R, Grimalt R. A review of platelet-rich plasma: History, biology, mechanism of action, and classification. Skin Appendage Dis 2018;4(1):18–24. PMCID: 5806188.
  14. Shen L, Yuan T, Chen S, et al. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res 2017;12(1):16. PMCID: 5260061.
  15. Si Z, Wang X, Sun C, et al. Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies. Biomed pharmacother 2019;114:108765. PMID: 30921703.
  16. Arthur A, Gronthos S. Clinical application of bone marrow mesenchymal stem/stromal cells to repair skeletal tissue. Int J Mol sc 2020;21(24):9759. PMCID: 7767389.
  17. Bar JK, Lis-Nawara A, Grelewski PG. Dental pulp stem cell-derived secretome and its regenerative potential. Int J Mol sci 2021;22(21): 12018. PMCID: 8584775.
  18. Pers YM, Rackwitz L, Ferreira R, et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: A phase I dose-escalation trial. Stem Cells Transl med 2016;5(7):847–856. PMCID: 4922848.
  19. McIntyre JA, Jones IA, Han B, et al. Intra-articular mesenchymal stem cell therapy for the human joint: A systematic review. Am J Sports Med 2018;46(14):3550–3563. PMID: 29099618.
  20. Yokota N, Hattori M, Ohtsuru T, et al. Comparative clinical outcomes after intra-articular injection with adipose-derived cultured stem cells or noncultured stromal vascular fraction for the treatment of knee osteoarthritis. Am J Sports Med 2019;47(11):2577–2583. PMID: 31373830.
  21. Mardones R, Jofre CM, Tobar L, et al. Mesenchymal stem cell therapy in the treatment of hip osteoarthritis. J Hip Preserv Surg 2017;4(2): 159–163. PMID: 28630737.
  22. Emadedin M, Ghorbani Liastani M, Fazeli R, et al. Long-term follow-up of intra-articular injection of autologous mesenchymal stem cells in patients with knee, ankle, or hip osteoarthritis. Arch Iran Med 2015;18(6):336–344. PMID: 26058927.
  23. Freitag J, Wickham J, Shah K, et al. Effect of autologous adipose-derived mesenchymal stem cell therapy in the treatment of acromioclavicular joint osteoarthritis. BMJ Case Rep 2019;12(2): e227865. PMCID: 6398814.
  24. Centeno CJ, Freeman MD. Percutaneous injection of autologous, culture-expanded mesenchymal stem cells into carpometacarpal hand joints: A case series with an untreated comparison group. Wien Med Wochenschr 2014;164(5-6):83–87. PMID: 23949564.
  25. Sfakianoudis K, Simopoulou M, Grigoriadis S, et al. Reactivating ovarian function through autologous platelet-rich plasma intraovarian infusion: Pilot data on premature ovarian insufficiency, perimenopausal, menopausal, and poor responder women. J Clin Med 2020;9(6):1809. PMCID: 7355907.
  26. Pettersson G, Andersen AN, Broberg P, et al. Pre-stimulation parameters predicting live birth after IVF in the long GnRH agonist protocol. Reprod biomed 2010;20(5):572–581. PMID: 20236862.
  27. Kasius A, Smit JG, Torrance HL, et al. Endometrial thickness and pregnancy rates after IVF: A systematic review and meta-analysis. Human reprod 2014;20(4):530–541. PMID: 24664156.
  28. Liu KE, Hartman M, Hartman A, et al. The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Human reprod 2018;33(10):1883–1888. PMCID: 6145412.
  29. Tandulwadkar SR, Naralkar MV, Surana AD, et al. Autologous intrauterine platelet-rich plasma instillation for suboptimal endometrium in frozen embryo transfer cycles: A pilot study. J Hum Reprod Sci 2017;10(3):208–212. PMCID: 5672727.
  30. Nazari L, Salehpour S, Hosseini MS, et al. The effects of autologous platelet-rich plasma in repeated implantation failure: A randomized controlled trial. Hum Fertil (Camb) 2020;23(3):209–213. PMID: 30714427.
  31. Mishra AK, Skrepnik NV, Edwards SG, et al. Efficacy of platelet-rich plasma for chronic tennis elbow: A double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med 2014;42(2):463–471. PMID: 23825183.
  32. Podesta L, Crow SA, Volkmer D, et al. Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma. Am J Sports Med 2013;41(7):1689–1694. PMID: 23666850.
  33. MS AH, Mohamed Ali MR, Yusof A, et al. Platelet-rich plasma injections for the treatment of hamstring injuries: A randomized controlled trial. Am J Sports Med 2014;42(10):2410–2418. PMID: 25073598.
  34. Fitzpatrick J, Bulsara M, Zheng MH. The effectiveness of platelet-rich plasma in the treatment of tendinopathy: A meta-analysis of randomized controlled clinical trials. Am J Sports Med 2017;45(1): 226–233. PMID: 27268111.
  35. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192(7):1027–1034. PMCID: 2193311.
  36. Melenhorst JJ, Chen GM, Wang M, et al. Author correction: Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells. Nature 2022;612(7941):E22. PMID: 36477542.
  37. Motohashi S, Iinuma T, Kurokawa T, et al. [Application of iPS Cell-Derived NKT Cells to Cancer Immunotherapy]. Gan to kagaku ryoho Cancer chemother 2020;47(10):1411–1414. PMID: 33130731.
  38. Yang YJ, Park JC, Kim HK, et al. A trial of autologous ex vivo-expanded NK cell-enriched lymphocytes with docetaxel in patients with advanced non-small cell lung cancer as second- or third-line treatment: phase IIa study. Anticancer Res 2013;33(5):2115–2122. PMID: 23645763.
  39. Firouzi N, Yavari HR, Rahimi S, et al. Concentrated growth factors combined with lipopolysaccharide stimulate the in vitro regenerative and osteogenic activities of human dental pulp stem cells by balancing inflammation. Int J dent 2022;2022:2316666. PMCID: 9780000.
  40. Chu J, Duan W, Yu Z, et al. Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis. Knee surg sports traumatol arthroscop 2022;30(12):4063–4071. PMID: 35124707.
  41. Russo F, D'Este M, Vadala G, et al. Platelet rich plasma and hyaluronic acid blend for the treatment of osteoarthritis: Rheological and biological evaluation. PloS one 2016;11(6):e0157048. PMCID: 4911091.
  42. Yamada M, Watanabe J, Ueno T, et al. Cytoprotective preconditioning of osteoblast-like cells with N-acetyl-L-cysteine for bone regeneration in cell therapy. Int J Mol sci 2019;20(20):5199. PMCID: 6834301.
  43. Anitua E. The use of plasma-rich growth factors (PRGF) in oral surgery. Pract Proced Aesthet Dent 2001;13(6):487–493. PMID: 11544821.
  44. Chilcott EM, Muiruri EW, Hirst TC, et al. Correction: Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models. Gene ther 2023;30(1-2):188. PMID: 36437357.
  45. Fu Z, Lai Y, Zhuang Y, et al. Injectable heat-sensitive nanocomposite hydrogel for regulating gene expression in the treatment of alcohol-induced osteonecrosis of the femoral head. APL Bioeng 2023;7(1):016107. PMCID: 9862308.
  46. Salehpour A, Balmagambetova S, Mussin N, et al. Mesenchymal stromal/stem cell-derived exosomes and genitourinary cancers: A mini review. Front Cell Development Biol 2022;10:1115786. PMCID: 9845763.
  47. Littig JPB, Moellmer R, Agrawal DK, et al. Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing. World J Diab 2023;14(1):35–47. PMCID: 9850797.
  48. Freeman FE, Browe DC, Nulty J, et al. Biofabrication of multiscale bone extracellular matrix scaffolds for bone tissue engineering. Eur cell mater 2019;38:168–187. PMID: 31602629.
  49. Nakatani Y, Agata H, Sumita Y, et al. Efficacy of freeze-dried platelet-rich plasma in bone engineering. Arch oral biol 2017;73:172–178. PMID: 27771585.
  50. Szablowska-Gadomska I, Rudzinski S, Dymowska M. Secretome of mesenchymal stromal cells as a possible innovative therapeutic tool in facial nerve injury treatment. BioMed res int 2023;2023:8427200. PMCID: 9867597.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.