Review

Center for Regenerative Medicine, Marriott Heart Disease Research Program, Van Cleve Cardiac Regenerative Medicine Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, 55905 MN, USA

Division of Geriatric Medicine & Gerontology, Department of Medicine, Mayo Clinic, Rochester, 55905 MN, USA

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Atta Behfar

https://orcid.org/0000-0003-3775-5784

Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, 55905 MN, USA

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Andre Terzic

*Author for correspondence: Tel.: +1 507 284 2747;

E-mail Address: terzic.andre@mayo.edu

https://orcid.org/0000-0001-9210-009X

Department of Molecular Pharmacology & Experimental Therapeutics, Department of Clinical Genomics, Mayo Clinic, Rochester, 55905 MN, USA

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Published Online:24 Feb 2021https://doi.org/10.2217/rme-2020-0178

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Abstract

Regenerative medicine, poised to transform 21st century healthcare, has aspired to enrich care options by bringing cures to patients in need. Science-driven responsible and regulated translation of innovative technology has enabled the launch of previously unimaginable care pathways adopted prudently for select serious diseases and disabilities. The collective resolve to advance the design, manufacture and validity of affordable regenerative solutions aims to democratize such health benefits for all. The objective of this Review is to outline the framework and prerequisites that underpin clinical readiness of regenerative care. Integrated research and development, specialized workforce education and accessible evidence-based practice implementation are at the core of realizing an equitable regenerative medicine vision.

Keywords:

Papers of special note have been highlighted as: • of interest

References

1. Terzic A, Nelson TJ. Regenerative medicine primer. Mayo Clin. Proc. 88(7), 766–775 (2013).
MedlineGoogle Scholar
2. Edgar L, Pu T, Porter B et al. Regenerative medicine, organ bioengineering and transplantation. Br. J. Surg. 107(7), 793–800 (2020).
Medline CASGoogle Scholar
3. Waldman SA, Terzic A. Bioinnovation Enterprise: an engine driving breakthrough therapies. Clin. Pharmacol. Ther. 99(1), 8–13 (2016).
Medline CASGoogle Scholar
4. Regenerative Medicine and RegMedNet. The glossary for advanced therapies. Regen. Med. 15(12s), 1–170 (2020).
MedlineGoogle Scholar
5. International Society for Stem Cell Research. Core concepts in stem cell biology: syllabus and learning guide. version 1, 1–49 (2020). http://www.isscr.org
Google Scholar
6. Cossu G, Fears R, Griffin G, Ter Meulen V. Regenerative medicine: challenges and opportunities. Lancet 395(10239), 1746–1747 (2020).
MedlineGoogle Scholar
7. Behfar A, Terzic A. Regeneration for all: an odyssey in biotherapy. Eur. Heart J. 40(13), 1033–1035 (2019).
MedlineGoogle Scholar
8. Terzic A, Harper CM Jr, Gores GJ, Pfenning MA. Regenerative medicine blueprint. Stem Cells Dev. 22(Suppl. 1), 20–24 (2013).
MedlineGoogle Scholar
9. Terzic A, Waldman SA. Chronic diseases: the emerging pandemic. Clin. Transl. Sci. 4(3), 225–226 (2011).
MedlineGoogle Scholar
10. U.S. Congress. 21st Century Cures Act Public Law. 114–255 (2016).
Google Scholar
11. Liu E, Marin D, Banerjee P et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N. Engl. J. Med. 382(6), 545–553 (2020).
Medline CASGoogle Scholar
12. June CH, Sadelain M. Chimeric antigen receptor therapy. N. Engl. J. Med. 379(1), 64–73 (2018). • Regenerative immunotherapy highlighted in the context of cancer care.
Medline CASGoogle Scholar
13. Beyar-Katz O, Gill S. Advances in chimeric antigen receptor T cells. Curr. Opin. Hematol. 27(6), 368–377 (2020).
Medline CASGoogle Scholar
14. McKay RR, Hafron JM, Ferro C et al. A retrospective observational analysis of overall survival with sipuleucel-T in medicare beneficiaries treated for advanced prostate cancer. Adv. Ther. 37(12), 4910–4929 (2020).
MedlineGoogle Scholar
15. Pellegrini G, Ardigò D, Milazzo G et al. Navigating market authorization: the path Holoclar took to become the first stem cell product approved in the European Union. Stem Cells Transl. Med. 7(1), 146–154 (2018).
MedlineGoogle Scholar
16. Panés J, García-Olmo D, Van Assche G et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology 154(5), 1334–1342.e4 (2018).
MedlineGoogle Scholar
17. Saris DBF, de Windt TS, Vonk LA, Krych AJ, Terzic A. Regenerative musculoskeletal care: ensuring practice implementation. Clin. Pharmacol. Ther. 103(1), 50–53 (2018).
MedlineGoogle Scholar
18. Bartunek J, Terzic A, Davison BA et al. Cardiopoietic stem cell therapy in ischaemic heart failure: long‐term clinical outcomes. ESC Heart Fail. 7(6), 3345–3354 (2020).
Google Scholar
19. Yanagi Y, Nakayama K, Taguchi T et al. In vivo and ex vivo methods of growing a liver bud through tissue connection. Sci. Rep. 7(1), 14085 (2017).
MedlineGoogle Scholar
20. Lee J, Rabbani CC, Gao H et al. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature 582(7812), 399–404 (2020). • New inroads of evolving regenerative technology for functional restoration.
Medline CASGoogle Scholar
21. Ibrahim AGE, Li C, Rogers R et al. Augmenting canonical Wnt signalling in therapeutically inert cells converts them into therapeutically potent exosome factories. Nat. Biomed. Eng. 3(9), 695–705 (2019).
Medline CASGoogle Scholar
22. Kang HW, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat. Biotechnol. 34(3), 312–319 (2016).
Medline CASGoogle Scholar
23. Martinod E, Chouahnia K, Radu DM et al. Feasibility of bioengineered tracheal and bronchial reconstruction using stented aortic matrices. JAMA 319(21), 2212–2222 (2018).
MedlineGoogle Scholar
24. Magalhaes RS, Williams JK, Yoo KW, Yoo JJ, Atala A. A tissue-engineered uterus supports live births in rabbits. Nat. Biotechnol. 38(11), 1280–1287 (2020).
Medline CASGoogle Scholar
25. Stevens MM, Marini RP, Schaefer D, Aronson J, Langer R, Shastri VP. In vivo engineering of organs: the bone bioreactor. Proc. Natl Acad. Sci. USA. 102(32), 11450–11455 (2005).
Medline CASGoogle Scholar
26. Martinod E, Paquet J, Dutau H et al. In vivo tissue engineering of human airways. Ann. Thorac. Surg. 103(5), 1631–1640 (2017).
MedlineGoogle Scholar
27. Service RF. Tissue engineering: technique uses body as ’bioreactor’ to grow new bone. Science 309(5735), 683 (2005).
Medline CASGoogle Scholar
28. Wells JM, Watt FM. Diverse mechanisms for endogenous regeneration and repair in mammalian organs. Nature 557(7705), 322–328 (2018). • Innate mechanisms of regeneration and repair are presented.
Medline CASGoogle Scholar
29. Hargraves IG, Behfar A, Foxen JL, Montori VM, Terzic A. Towards regeneration: the evolution of medicine from fighting to building. BMJ 361, k1586 (2018).
Google Scholar
30. Wyles SP, Terzic A. Building the regenerative medicine workforce of the future: an educational imperative. Regen. Med. 14(7), 613–615 (2019).
CASGoogle Scholar
31. Chlan LL, Tofthagen C, Terzic A. The regenerative horizon: opportunities for nursing research and practice. J. Nurs. Scholarsh. 51(6), 651–660 (2019).
MedlineGoogle Scholar
32. Wyles SP, Hayden RE, Meyer FB, Terzic A. Regenerative medicine curriculum for next-generation physicians. NPJ Regen. Med. 4, 3 (2019).
MedlineGoogle Scholar
33. Wyles SP, Meyer FB, Hayden R, Scarisbrick I, Terzic A. Digital regenerative medicine and surgery pedagogy for virtual learning in the time of COVID-19. Regen. Med. 15(8), 1937–1941 (2020).
CASGoogle Scholar
34. Sharma A, McKeithan WL, Serrano R et al. Use of human induced pluripotent stem cell-derived cardiomyocytes to assess drug cardiotoxicity. Nat. Protoc. 13(12), 3018–3041 (2018).
Medline CASGoogle Scholar
35. Ronaldson-Bouchard K, Yeager K, Teles D et al. Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype. Nat. Protoc. 14(10), 2781–2817 (2019).
Medline CASGoogle Scholar
36. Tysoe OC, Justin AW, Brevini T et al. Isolation and propagation of primary human cholangiocyte organoids for the generation of bioengineered biliary tissue. Nat. Protoc. 14(6), 1884–1925 (2019).
Medline CASGoogle Scholar
37. Jacob F, Ming GL, Song H. Generation and biobanking of patient-derived glioblastoma organoids and their application in CAR T cell testing. Nat. Protoc. 15(12), 4000–4033 (2020).
Medline CASGoogle Scholar
38. Bansal A, Pandey MK, Yamada S et al. [⁸⁹Zr]Zr-DBN labeled cardiopoietic stem cells proficient for heart failure. Nucl. Med. Biol. 90-91, 23–30 (2020).
Medline CASGoogle Scholar
39. Sanicola HW, Stewart CE, Mueller M et al. Guidelines for establishing a 3-D printing biofabrication laboratory. Biotechnol. Adv. 45, 107652 (2020).
Medline CASGoogle Scholar
40. Terzic A, Pfenning MA, Gores GJ, Harper CM Jr. Regenerative medicine build-out. Stem Cells Transl. Med. 4(12), 1373–1379 (2015). • Prototype for institutional regenerative medicine readiness.
MedlineGoogle Scholar
41. Nelson TJ, Behfar A, Yamada S, Martinez-Fernandez A, Terzic A. Stem cell platforms for regenerative medicine. Clin. Transl. Sci. 2(3), 222–227 (2009).
Medline CASGoogle Scholar
42. Hunsberger J, Harrysson O, Shirwaiker R et al. Manufacturing road map for tissue engineering and regenerative medicine technologies. Stem Cells Transl. Med. 4(2), 130–135 (2015).
MedlineGoogle Scholar
43. Hunsberger J, Simon C, Zylberberg C et al. Improving patient outcomes with regenerative medicine: How the Regenerative Medicine Manufacturing Society plans to move the needle forward in cell manufacturing, standards, 3D bioprinting, artificial intelligence-enabled automation, education, and training. Stem Cells Transl. Med. 9(7), 728–733 (2020).
MedlineGoogle Scholar
44. Smith C, Martin-Lillie C, Higano JD et al. Challenging misinformation and engaging patients: characterizing a regenerative medicine consult service. Regen. Med. 15(3), 1427–1440 (2020).
CASGoogle Scholar
45. Terzic A, Edwards BS, McKee KC, Nelson TJ. Regenerative medicine: a reality of stem cell technology. Minn. Med. 94(5), 44–47 (2011).
MedlineGoogle Scholar
46. Waldman SA, Terzic A. Companion diagnostics at the intersection of personalized medicine and healthcare delivery. Biomark. Med. 9(1), 1–3 (2015).
CASGoogle Scholar
47. Yamada S, Jeon R, Garmany A, Behfar B, Terzic A. Screening for regenerative therapy responders in heart failure. Biomark. Med. (Epub ahead of print) (2021).
Google Scholar
48. Rieger AC, Myerburg RJ, Florea V et al. Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy. EBioMedicine 48, 377–385 (2019).
Medline CASGoogle Scholar
49. Bartunek J, Terzic A, Behfar A, Wijns W. Clinical experience with regenerative therapy in heart failure: advancing care with cardiopoietic stem cell interventions. Circ. Res. 122(10), 1344–1346 (2018).
Medline CASGoogle Scholar
50. Frljak S, Poglajen G, Zemljic G et al. Larger end-diastolic volume associates with response to cell therapy in patients with non-ischemic dilated cardiomyopathy. Mayo Clin. Proc. 95(10), 2125–2133 (2020).
Medline CASGoogle Scholar
51. Yamada S, Arrell DK, Rosenow CS, Bartunek J, Behfar A, Terzic A. Ventricular remodeling in ischemic heart failure stratifies responders to stem cell therapy. Stem Cells Transl. Med. 9(1), 74–79 (2020).
MedlineGoogle Scholar
52. De Luca M, Aiuti A, Cossu G et al. Advances in stem cell research and therapeutic development. Nat. Cell Biol. 21, 801–811 (2019).
MedlineGoogle Scholar
53. Lomax GP, Torres A, Millan MT. Regulated, reliable, and reputable: protect patients with uniform standards for stem cell treatments. Stem Cells Transl. Med. 9(5), 547–553 (2020).
MedlineGoogle Scholar
54. Gardner J. Distributive justice and regenerative medicine. Regen. Med. 12(7), 865–874 (2017).
CASGoogle Scholar
55. Cho E, Yoo SL, Kang Y, Lee JH. Reimbursement and pricing of regenerative medicine in South Korea: key factors for achieving reimbursement. Regen. Med. 15(4), 1550–1560 (2020).
CASGoogle Scholar
56. Coyle D, Durand-Zaleski I, Farrington J et al. HTA methodology and value frameworks for evaluation and policy making for cell and gene therapies. Eur. J. Health Econ. 21(9), 1421–1437 (2020).
MedlineGoogle Scholar
57. Thavorn K, Van Katwyk S, Krahn M et al. Value of mesenchymal stem cell therapy for patients with septic shock: an early health economic evaluation. Int. J. Technol. Assess. Health Care. 36(5), 525–532 (2020).
MedlineGoogle Scholar
58. Marks P, Gottlieb S. Balancing safety and innovation for cell-based regenerative medicine. N. Engl. J. Med. 378(10), 954–959 (2018). • The US FDA perspective on regenerative medicine regulatory path.
MedlineGoogle Scholar
59. Elsallab M, Bravery CA, Kurtz A, Abou-El-Enein M. Mitigating deficiencies in evidence during regulatory assessments of advanced therapies: a comparative study with other biologicals. Mol. Ther. Methods Clin. Dev. 18, 269–279 (2020).
Medline CASGoogle Scholar
60. Bandeiras C, Hwa AJ, Cabral JMS, Ferreira FC, Finkelstein SN, Gabbay RA. Economics of beta-cell replacement therapy. Curr. Diab. Rep. 19(9), 75 (2019).
MedlineGoogle Scholar
61. Patel NA. Fee-for-value in the pharmaceutical industry: a policy framework applying data science to negotiate drug prices. J. Law Biosci. 4(1), 205–215 (2017).
MedlineGoogle Scholar
62. Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature 561(7721), 45–56 (2018).
Medline CASGoogle Scholar
63. Tchkonia T, Kirkland JL. Aging, cell senescence, and chronic disease: emerging therapeutic strategies. JAMA 320(13), 1319–1320 (2018).
MedlineGoogle Scholar
64. Olshansky SJ. From lifespan to healthspan. JAMA 320(13), 1323–1324 (2018).
MedlineGoogle Scholar
65. van Deursen JM. Senolytic therapies for healthy longevity. Science 364(6441), 636–637 (2019).
Medline CASGoogle Scholar
66. Roth GA, Mensah GA, Johnson CO et al. GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. J. Am. Coll. Cardiol. 76(25), 2982–3021 (2020).
MedlineGoogle Scholar
67. Waldman SA, Terzic A. Health care evolves from reactive to proactive. Clin. Pharmacol. Ther. 105(1), 10–13 (2019).
MedlineGoogle Scholar
68. Nelson TJ, Behfar A, Terzic A. Strategies for therapeutic repair: the R³ regenerative medicine paradigm. Clin. Transl. Sci. 1(2), 168–171 (2008).
MedlineGoogle Scholar
69. Yamanaka S. Pluripotent stem cell-based cell therapy: promise and challenges. Cell Stem Cell. 27(4), 523–531 (2020).
Medline CASGoogle Scholar
70. Huang RL, Kobayashi E, Liu K, Li Q, Huang RL. Bone graft prefabrication following the in vivo bioreactor principle. EBioMedicine. 12, 43–54 (2016).
MedlineGoogle Scholar
71. Hoffman T, Khademhosseini A, Langer R. Chasing the paradigm: clinical translation of 25 years of tissue engineering. Tissue Eng. Part A. 25(9-10), 679–687 (2019).
MedlineGoogle Scholar
72. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20(2), 101–124 (2021).
Medline CASGoogle Scholar
73. Gensler M, Leikeim A, Möllmann M et al. 3D printing of bioreactors in tissue engineering: a generalised approach. PLoS ONE 15(11), e0242615 (2020).
Medline CASGoogle Scholar
74. Fuchs E, Blau HM. Tissue stem cells: architects of their niches. Cell Stem Cell. 27(4), 532–556 (2020).
Medline CASGoogle Scholar
75. Marks PW, Hahn S. Identifying the risks of unproven regenerative medicine therapies. JAMA 324(3), 241–242 (2020).
MedlineGoogle Scholar
76. Matsushita S, Tachibana K, Kusakabe T, Hirayama R, Tsutsumi Y, Kondoh M. The roadmap to approval under Japan’s two-track regulatory system: comparing six regenerative medical products. Cell Stem Cell. 27(4), 515–518 (2020).
Medline CASGoogle Scholar
77. Nagai S. Flexible and expedited regulatory review processes for innovative medicines and regenerative medical products in the US, the EU, and Japan. Int. J. Mol. Sci. 20(15), 3801 (2019).
CASGoogle Scholar
78. Wyles SP, Morie DD, Paradise CR, Meyer FB, Hayden RE, Terzic A. Emerging workforce readiness in regenerative healthcare. Regen. Med. 10.2217/rme-2020-0137 (2021) (Submitted).
Google Scholar
79. King NMP, Bishop CE. How should physicians help patients understand unknowns of nanoparticle-based medicines? AMA. J. Ethics. 21(4), E324–E331 (2019).
MedlineGoogle Scholar
80. Master Z, Crowley AP, Smith C, Wigle D, Terzic A, Sharp RR. Stem cell preservation for regenerative therapies: ethical and governance considerations for the health care sector. NPJ Regen. Med. 5(1), 23 (2020).
MedlineGoogle Scholar
81. Karanu F, Ott L, Webster DA, Stehno-Bittel L. Improved harmonization of critical characterization assays across cell therapies. Regen. Med. 15(5), 1661–1678 (2020).
CASGoogle Scholar
82. Doulgkeroglou MN, Di Nubila A, Niessing B et al. Automation, monitoring, and standardization of cell product manufacturing. Front. Bioeng. Biotechnol. 8, 811 (2020).
MedlineGoogle Scholar
83. Terzic A, Behfar A, Filippatos G. Clinical development plan for regenerative therapy in heart failure. Eur. J. Heart Fail. 18(2), 142–144 (2016).
MedlineGoogle Scholar
84. Terzic A, Behfar A. Posology for regenerative therapy. Circ. Res. 121(11), 1213–1215 (2017).
Medline CASGoogle Scholar
85. Driscoll D, Farnia S, Kefalas P, Maziarz RT. The high cost of high tech medicine: planning ahead for market access. Stem Cells Transl. Med. 6(8), 1723–1729 (2017).
MedlineGoogle Scholar
86. Gonçalves E. Advanced therapy medicinal products: value judgement and ethical evaluation in health technology assessment. Eur. J. Health Econ. 21(3), 311–320 (2020).
MedlineGoogle Scholar
87. Llorens-Bobadilla E, Chell JM, Le Merre P et al. A latent lineage potential in resident neural stem cells enables spinal cord repair. Science 370(6512), eabb8795 (2020).
Medline CASGoogle Scholar
88. Yokota T, McCourt J, Ma F et al. Type V collagen in scar tissue regulates the size of scar after heart injury. Cell 182(3), 545–562.e23 (2020).
Medline CASGoogle Scholar
89. Kim E, Choi S, Kang B et al. Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature 588(7839), 664–669 (2020).
Medline CASGoogle Scholar
90. Nikolaev M, Mitrofanova O, Broguiere N et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 585(7826), 574–578 (2020).
MedlineGoogle Scholar
91. Chaudhuri O, Cooper-White J, Janmey PA, Mooney DJ, Shenoy VB. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584(7822), 535–546 (2020).
Medline CASGoogle Scholar
92. Doudna JA. The promise and challenge of therapeutic genome editing. Nature 578(7794), 229–236 (2020).
Medline CASGoogle Scholar
93. Terzic A, Leask F. Regenerative outlook: offering global solutions for equity of care. Regen. Med. 15(11), 2249–2252 (2020).
Google Scholar
94. Blau HM, Daley GQ. Stem cells in the treatment of disease. N. Engl. J. Med. 380(18), 1748–1760 (2019).
Medline CASGoogle Scholar
95. Fioretta ES, Motta SE, Lintas V et al. Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity. Nat. Rev. Cardiol. 18(2), 92–116 (2021).
MedlineGoogle Scholar
96. Wu JC, Garg P, Yoshida Y et al. Towards precision medicine with human iPSCs for cardiac channelopathies. Circ. Res. 125(6), 653–658 (2019).
Medline CASGoogle Scholar
97. Schaum N, Lehallier B, Hahn O et al. Ageing hallmarks exhibit organ-specific temporal signatures. Nature 583(7817), 596–602 (2020).
Medline CASGoogle Scholar
98. Rajewsky N, Almouzni G, Gorski SA et al. LifeTime and improving European healthcare through cell-based interceptive medicine. Nature 587(7834), 377–386 (2020).
Medline CASGoogle Scholar
99. West MD, Sternberg H, Labat I et al. Toward a unified theory of aging and regeneration. Regen. Med. 14(9), 867–886 (2019). • Intersections unifying aging biology and regeneration.
CASGoogle Scholar
100. Correa-Gallegos D, Jiang D, Christ S et al. Patch repair of deep wounds by mobilized fascia. Nature 576(7786), 287–292 (2019).
Medline CASGoogle Scholar
101. Hirose K, Payumo AY, Cutie S et al. Evidence for hormonal control of heart regenerative capacity during endothermy acquisition. Science 364(6436), 184–188 (2019).
Medline CASGoogle Scholar
102. Liu X, Ouyang JF, Rossello FJ et al. Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature 586(7827), 101–107 (2020). • Dissection of regenerative programs at cell fate level.
Medline CASGoogle Scholar
103. Arrell DK, Rosenow CS, Yamada S, Behfar A, Terzic A. Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome. NPJ Regen. Med. 5, 5 (2020).
Medline CASGoogle Scholar
104. Becker SM, Wright CB. Update on the status and impact of the National Eye Institute audacious goals initiative for regenerative medicine. J. Ocul. Pharmacol. Ther. doi: 10.1089/jop.2020.0015 (2020) (Epub ahead of print).
Google Scholar
105. Webster A. Regenerative medicine and responsible research and innovation: proposals for a responsible acceleration to the clinic. Regen. Med. 12(7), 853–864 (2017). • Perspective on responsible acceleration of regenerative medicine.
CASGoogle Scholar
106. Gardner J, Webster A, Barry J. Anticipating the clinical adoption of regenerative medicine: building institutional readiness in the UK. Regen. Med. 13(1), 29–39 (2018).
CASGoogle Scholar
107. Shapiro SA, Smith CG, Arthurs JR, Master Z. Preparing regenerative therapies for clinical application: proposals for responsible translation. Regen. Med. 14(2), 77–84 (2019).
CASGoogle Scholar
108. Waldman SA, Terzic A. Process improvement for maximized therapeutic innovation outcome. Clin. Pharmacol. Ther. 103(1), 8–12 (2018).
Medline CASGoogle Scholar
109. Terzic A. Regenerative medicine lexicon. Regen. Med. 15(12), 2325–2328 (2020).
CASGoogle Scholar
110. Evans MK. Health equity - are we finally on the edge of a new frontier? N. Engl. J. Med. 383(11), 997–999 (2020).
MedlineGoogle Scholar
111. Gardner J, Higham R, Faulkner A, Webster A. Promissory identities: sociotechnical representations & innovation in regenerative medicine. Soc. Sci. Med. 174, 70–78 (2017).
MedlineGoogle Scholar
112. Gostin LO, DeBartolo MC, Katz R. The global health law trilogy: towards a safer, healthier, and fairer world. Lancet 390(10105), 1918–1926 (2017).
MedlineGoogle Scholar
113. Fernández-Avilés F, Sanz-Ruiz R, Climent AM et al. Global position paper on cardiovascular regenerative medicine. Eur. Heart J. 38(33), 2532–2546 (2017).
Medline CASGoogle Scholar
114. Behfar A, Terzic A. Make regeneration great again; stronger together. Eur. Heart J. 38(15), 1094–1095 (2017).
MedlineGoogle Scholar
115. Ramezankhani R, Torabi S, Minaei N et al. Two decades of global progress in authorized advanced therapy medicinal products: an emerging revolution in therapeutic strategies. Front. Cell. Dev. Biol. 8, 547653 (2020).
MedlineGoogle Scholar

Vol. 16, No. 3

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History

Received 17 November 2020

Accepted 5 February 2021

Published online 24 February 2021

Published in print March 2021

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Keywords

Author contributions

S Yamada, A Behfar and A Terzic were responsible for the conception and design, data acquisition, analysis and interpretation, drafting the work, final approval of the manuscript, financial and administrative support, and agreement to be accountable for all aspects of the work.

Acknowledgments

The authors acknowledge Adam Price-Evans (a former employee of Future Science Group, was the Commissioning Editor for Regenerative Medicine at the time of writing) for his invaluable discussion and input. A Terzic holds the Marriott Family Professorship in Cardiovascular Diseases Research, and is Michael S. and Mary Sue Shannon Director of the Mayo Clinic Center for Regenerative Medicine.

Financial & competing interests disclosure

The authors are supported by the National Institutes of Health (R01 HL134664), Marriott Family Foundation, Van Cleve Cardiac Regenerative Medicine Program, Michael S. and Mary Sue Shannon Family, and Center for Regenerative Medicine at Mayo Clinic. S Yamada, A Behfar and A Terzic are coinventors on regenerative sciences related intellectual property disclosed to Mayo Clinic. Previously, Mayo Clinic has administered research grants from Celyad. Mayo Clinic, A Behfar and A Terzic have interests in Rion LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Regenerative medicine clinical readiness

Abstract

References