Skip to main content

Advertisement

SpringerLink
Log in

Regenerative medicine: the red planet for clinicians

  • IM - REVIEW
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Regenerative medicine represents the forefront of health sciences and holds promises for the treatment and, possibly, the cure of a number of challenging conditions. It relies on the use of stem cells, tissue engineering, and gene therapy alone or in different combinations. The goal is to deliver cells, tissues, or organs to repair, regenerate, or replace the damaged ones. Among stem-cell populations, both haematopoietic and mesenchymal stem cells have been employed in the treatment of refractory chronic inflammatory diseases with promising results. However, only mesenchymal stem cells seem advantageous as both systemic and local injections may be performed without the need for immune ablation. Recently, also induced pluripotent stem cells have been exploited for therapeutic purposes given their tremendous potential to be an unlimited source of any tissue-specific cells. Moreover, through the development of technologies that make organ fabrication possible using cells and supporting scaffolding materials, regenerative medicine promises to enable organ-on-demand, whereby patients will receive organs in a timely fashion without the risk of rejection. Finally, gene therapy is emerging as a successful strategy not only in monogenic diseases, but also in multifactorial conditions. Several of these approaches have recently received approval for commercialization, thus opening a new therapeutic era. This is why both General Practitioners and Internists should be aware of these great advancements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AAV:

Adeno-associated viral

ADA:

Adenosine deaminase deficiency

AdV:

Adenoviral

CAR:

Chimeric antigen receptor

ECM:

Extracellular matrix

ESC:

Embryonic stem cells

HSC:

Haematopoietic stem cells

iPSC:

Induced pluripotent stem cells

LV:

Lentiviral vector

MSC:

Mesenchymal stem cells

RM:

Regenerative medicine

RV:

Gammaretroviral vector

SCID:

Severe combined immune-deficiency

SMA:

Spinal muscular atrophy

References

  1. Orlando G, Murphy S, Bussolati B, Clancy M, Cravedi P, Migliaccio G, Murray P (2018) Rethinking regenerative medicine from a transplant perspective (and vice versa). Transplantation. https://doi.org/10.1097/tp.0000000000002370

    Article  PubMed  PubMed Central  Google Scholar 

  2. Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926

    Article  CAS  PubMed  Google Scholar 

  3. Orlando G, Soker S, Stratta RJ (2013) Organ bioengineering and regeneration as the new holy grail for organ transplantation. Ann Surg 258:221–232. https://doi.org/10.1097/SLA.0b013e31829c79cf

    Article  PubMed  Google Scholar 

  4. Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H et al (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12:459–465

    Article  CAS  PubMed  Google Scholar 

  5. Ohashi K, Yokoyama T, Yamato M, Kuge H, Kanehiro H, Tsutsumi M et al (2007) Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets. Nat Med 13:880–885

    Article  CAS  PubMed  Google Scholar 

  6. Tsuda Y, Kikuchi A, Yamato M, Sakurai Y, Umezu M, Okano T (2004) Control of cell adhesion and detachment using temperature and thermoresponsive copolymer grafted culture surfaces. J Biomed Mater Res A 69:70–78

    Article  CAS  PubMed  Google Scholar 

  7. Kobayashi J, Akiyama Y, Yamato M, Shimizu T, Okano T (2018) Design of temperature-responsive cell culture surfaces for cell sheet-based regenerative therapy and 3D tissue fabrication. Adv Exp Med Biol 1078:371–393. https://doi.org/10.1007/978-981-13-0950-2_19

    Article  CAS  PubMed  Google Scholar 

  8. Saldin LT, Cramer MC, Velankar SS, White LJ, Badylak SF (2017) Extracellular matrix hydrogels from decellularized tissues: structure and function. Acta Biomater 49:1–15. https://doi.org/10.1016/j.actbio.2016.11.068

    Article  CAS  PubMed  Google Scholar 

  9. Nieponice A, Ciotola FF, Nachman F, Jobe BA, Hoppo T, Londono R et al (2014) Patch esophagoplasty: esophageal reconstruction using biologic scaffolds. Ann Thorac Surg 97:283–288. https://doi.org/10.1016/j.athoracsur.2013.08.011

    Article  PubMed  Google Scholar 

  10. Urban L, Camilli C, Phylactopoulos DE, Crowley C, Natarajan D, Scottoni F et al (2018) Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors. Nat Commun 9:4286. https://doi.org/10.1038/s41467-018-06385-w

    Article  CAS  Google Scholar 

  11. Thompson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS et al (1998) Embryonic stem cell lines derived from human blastocyst. Science 282:1145–1147

    Article  Google Scholar 

  12. Knoepfler PS (2009) Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells 27:1050–1056. https://doi.org/10.1002/stem.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ et al (2015) Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet 385:509–516. https://doi.org/10.1016/S0140-6736(14)61376-3

    Article  PubMed  Google Scholar 

  14. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  15. Guyette JP, Charest JM, Mills RW, Jank BJ, Moser PT, Gilpin SE et al (2016) Bioengineering human myocardium on native extracellular matrix. Circ Res 118:56–72. https://doi.org/10.1161/CIRCRESAHA.115.306874

    Article  CAS  PubMed  Google Scholar 

  16. Wilm B, Tamburrini R, Orlando G, Murray P (2016) Autologous cells for kidney bioengineering. Curr Transplant Rep 3:207–220

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang B, Jakus AE, Baptista PM, Soker S, Soto-Gutierrez A, Abecassis MM et al (2016) Functional maturation of induced pluripotent stem cell hepatocytes in extracellular matrix-a comparative analysis of bioartificial liver microenvironments. Stem Cells Transl Med 5:1257–1267. https://doi.org/10.5966/sctm.2015-0235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wan J, Huang Y, Zhou P, Guo Y, Wu C, Zhu S et al (2017) Culture of iPSCs derived pancreatic beta-like cells in vitro using decellularized pancreatic scaffolds: a preliminary trial. Biomed Res Int 2017:4276928. https://doi.org/10.1155/2017/4276928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C et al (2015) Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526:564–568. https://doi.org/10.1038/nature15695

    Article  CAS  PubMed  Google Scholar 

  20. Múnera JO, Sundaram N, Rankin SA, Hill D, Watson C, Mahe M et al (2017) Differentiation of human pluripotent stem cells into colonic organoids via transient activation of BMP signaling. Cell Stem Cell 21:51.e6–64.e6. https://doi.org/10.1016/j.stem.2017.05.020

    Article  CAS  Google Scholar 

  21. Kumar D, Anand T, Kues WA (2017) Clinical potential of human-induced pluripotent stem cells: perspectives of induced pluripotent stem cells. Cell Biol Toxicol 33:99–112. https://doi.org/10.1007/s10565-016-9370-9

    Article  CAS  PubMed  Google Scholar 

  22. Yoshihara M, Hayashizaki Y, Murakawa Y (2017) Genomic instability of iPSCs: challenges towards their clinical applications. Stem Cell Rev 13:7–16. https://doi.org/10.1007/s12015-016-9680-6

    Article  CAS  Google Scholar 

  23. Crook JM, Hei D, Stacey G (2010) The International Stem Cell Banking Initiative (ISCBI): raising standards to bank on. Vitro Cell Dev Biol Anim 46:169–172. https://doi.org/10.1007/s11626-010-9301-7

    Article  Google Scholar 

  24. Kim JH, Kurtz A, Yuan BZ, Zeng F, Lomax G, Loring JF et al (2017) Report of the International Stem Cell Banking Initiative Workshop activity: current hurdles and progress in seed-stock banking of human pluripotent stem cells. Stem Cells Transl Med 6:1956–1962. https://doi.org/10.1002/sctm.17-0144

    Article  PubMed  PubMed Central  Google Scholar 

  25. Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J et al (2010) Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica 95:284–292. https://doi.org/10.3324/haematol.2009.013458

    Article  PubMed  Google Scholar 

  26. Hawkey CJ, Allez M, Clark MM, Labopin M, Lindsay JO, Ricart E et al (2015) Autologous hematopoetic stem cell transplantation for refractory Crohn disease: a randomized clinical trial. JAMA 314:2524–2534. https://doi.org/10.1001/jama.2015.16700

    Article  CAS  PubMed  Google Scholar 

  27. Sun JM, Kurtzberg J (2018) Cell therapy for diverse central nervous system disorders: inherited metabolic diseases and autism. Pediatr Res 83:364–371. https://doi.org/10.1038/pr.2017.254

    Article  CAS  PubMed  Google Scholar 

  28. Martino M, Lanza F, Pavesi L, Öztürk M, Blaise D, Leno Núñez R et al (2016) High-dose chemotherapy and autologous hematopoietic stem cell transplantation as adjuvant treatment in high-risk breast cancer: data from the European Group for Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 22:475–481. https://doi.org/10.1016/j.bbmt.2015.12.011

    Article  PubMed  Google Scholar 

  29. Slatter MA, Gennery AR (2018) Hematopoietic cell transplantation in primary immunodeficiency—conventional and emerging indications. Expert Rev Clin Immunol 14:103–114. https://doi.org/10.1080/1744666X.2018.1424627

    Article  CAS  PubMed  Google Scholar 

  30. Leventhal JR, Ildstad ST (2018) Tolerance induction in HLA disparate living donor kidney transplantation by facilitating cell-enriched donor stem cell infusion: the importance of durable chimerism. Hum Immunol 79:272–276. https://doi.org/10.1016/j.humimm.2018.01.007

    Article  PubMed  Google Scholar 

  31. Charbord P (2010) Bone marrow mesenchymal stem cells: historical overview and concepts. Human Gene Ther 21:1045–1056

    Article  CAS  Google Scholar 

  32. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  CAS  PubMed  Google Scholar 

  33. Griffin MD, Elliman SJ, Cahill E, English K, Ceredig R, Ritter T (2013) Concise review: adult mesenchymal stromal cell therapy for inflammatory diseases: how well are we joining the dots? Stem Cells 31:2033–2041. https://doi.org/10.1002/stem.1452

    Article  CAS  PubMed  Google Scholar 

  34. Regulski MJ (2017) Mesenchymal stem cells: “guardians of inflammation”. Wounds 29:20–27

    PubMed  Google Scholar 

  35. Sundin M, Ringdén O, Sundberg B, Nava S, Götherström C, Le Blanc K (2007) No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 92:1208–1215

    Article  CAS  PubMed  Google Scholar 

  36. Galipeau J, Sensébe L (2018) Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 22:824–833. https://doi.org/10.1016/j.stem.2018.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ankrum JA, Ong JF, Karp JM (2014) Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 32:252–260. https://doi.org/10.1038/nbt.2816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Shing Cheung T et al (2017) Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci Transl Med 9:eaam7828. https://doi.org/10.1126/scitranslmed.aam7828

    Article  CAS  PubMed  Google Scholar 

  39. Le Blank C, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441

    Article  Google Scholar 

  40. Chen X, Wang C, Yin J, Xu J, Wei J, Zhang Y (2015) Efficacy of mesenchymal stem cell therapy for steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. PLoS One 10:e0136991. https://doi.org/10.1371/journal.pone.0136991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang L-T, Ting C-H, Yen M-L, Liu KJ, Sytwu HK, Wu KK, Yen BL (2016) Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated disease: review of current clinical trials. J Biomed Sci 23:76. https://doi.org/10.1186/s12929-016-0289-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC et al (2016) Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet 388:1281–1290. https://doi.org/10.1016/S0140-6736(16)31203-X

    Article  PubMed  Google Scholar 

  43. Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC et al (2012) Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 7:e47559. https://doi.org/10.1371/journal.pone.0047559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Toyserkani NM, Jørgensen MG, Tabatabaeifar S, Jensen CH, Sheikh SP, Sørensen JA (2017) Concise review: a safety assessment of adipose-derived cell therapy in clinical trials: a systematic review of reported adverse events. Stem Cells Transl Med 6:1786–1794. https://doi.org/10.1002/sctm.17-0031

    Article  PubMed  PubMed Central  Google Scholar 

  45. Spees JL, Lee RH, Gregory CA (2016) Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther 7:125. https://doi.org/10.1186/s13287-016-0363-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, Debruijn J et al (2016) International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy 18:151–159. https://doi.org/10.1016/j.jcyt.2015.11.008

    Article  CAS  PubMed  Google Scholar 

  47. Pellegrini G, Ardigò D, Milazzo G, Iotti G, Guatelli P, Pelosi D, De Luca M (2018) Navigating market authorization: the path holoclar took to become the first stem cell product approved in the European Union. Stem Cell Transl Med 7:146–154. https://doi.org/10.1002/sctm.17-0003

    Article  Google Scholar 

  48. Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L et al (2017) Regeneration of the entire human epidermis using transgenic stem cells. Nature 551:327–332. https://doi.org/10.1038/nature24487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M (2018) Gene therapy comes of age. Science. https://doi.org/10.1126/science.aan4672

    Article  PubMed  Google Scholar 

  50. Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ (2017) Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med 9:1183–1197. https://doi.org/10.15252/emmm.201607485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bl Davidson, McCray PB Jr (2011) Current prospects for RNA interference-based therapies. Nat Rev Genet 12:329–340. https://doi.org/10.1038/nrg2968

    Article  CAS  Google Scholar 

  52. Amabile A, Migliara A, Capasso P, Biffi M, Cittaro D, Naldini L, Lombardo A (2016) Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing. Cell 167:219–232. https://doi.org/10.1016/j.cell.2016.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V et al (2010) Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR53 control HIV-1 in vivo. Nat Biotechnol 28:839–847. https://doi.org/10.1038/nbt.1663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Maeder ML, Gersbach CA (2016) Genome-editing technologies for gene and cell therapy. Mol Ther 24:430–446. https://doi.org/10.1038/mt.2016.10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kosicki M, Tomberg K, Bradley A (2018) Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol 36:765–771. https://doi.org/10.1038/nbt.4192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Schiroli G, Conti A, Ferrari S, Della Volpe L, Jacob A, Albano L, Beretta S, Calabria A, Vavassori V, Gasparini P, Salataj E, Ndiaye-Lobry D, Brombin C, Chaumeil J, Montini E, Merelli I, Genovese P, Naldini L, Di Micco R (2019) Precise gene editing preserves hematopoietic stem cell function following transient p53-mediated DNA damage response. Cell Stem Cell 24:551–565. https://doi.org/10.1016/j.stem.2019.02.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Biasco L, Rothe M, Büning H, Schambach A (2017) Analyzing the genotoxicity of retroviral vectors in hematopoietic cell gene therapy. Mol Ther Methods Clin Dev 8:21–30. https://doi.org/10.1016/j.omtm.2017.10.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Annoni A, Gregori S, Naldini L, Cantore A (2018) Modulation of immune responses in lentiviral vector-mediated gene transfer. Cell Immunol pii. https://doi.org/10.1016/j.cellimm.2018.04.012

    Article  Google Scholar 

  59. Ferrua F, Aiuti A (2017) Twenty-five years of gene therapy for ADA-SCID: from bubble babies to an approved drug. Hum Gene Ther 28:972–981. https://doi.org/10.1089/hum.2017.175

    Article  CAS  PubMed  Google Scholar 

  60. Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C et al (2013) Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 341:1233151. https://doi.org/10.1126/science.1233151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sessa M, Lorioli L, Fumagalli F, Acquati S, Redaelli D, Baldoli C et al (2016) Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet 388:476–487. https://doi.org/10.1016/S0140-6736(16)30374-9

    Article  CAS  PubMed  Google Scholar 

  62. Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S et al (2018) Gene therapy in patients with transfusion-dependent β-thalassemia. N Engl J Med 378:1479–1493. https://doi.org/10.1056/NEJMoa1705342

    Article  CAS  PubMed  Google Scholar 

  63. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ et al (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371:1507–1517. https://doi.org/10.1056/NEJMoa1407222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ et al (2016) T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 128:1688–1700. https://doi.org/10.1182/blood-2016-04-711903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M et al (2009) Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I–II study. Lancet Oncol 10:489–500. https://doi.org/10.1016/S1470-2045(09)70074-9

    Article  PubMed  Google Scholar 

  66. Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F et al (2009) Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet 374:1597–1605. https://doi.org/10.1016/S0140-6736(09)61836-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J et al (2017) Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med 377:2215–2227. https://doi.org/10.1056/NEJMoa1708538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mendell JR (2018) Therapy for spinal muscular atrophy. N Engl J Med 378:487. https://doi.org/10.1056/NEJMc1715769

    Article  PubMed  Google Scholar 

  69. Palfi S, Gurruchaga JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC et al (2014) Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation, open-label, phase 1/2 trial. Lancet 383:1138–1146. https://doi.org/10.1016/S0140-6736(13)61939-X

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Professor Gino Roberto Corazza and Professor Luigi Naldini for helpful and constructive discussion.

Funding

No fund was used to prepare the manuscript.

Author information

Authors and Affiliations

  1. Gastroenterology Unit, Department of Medicine, AOUI Policlinico G.B. Rossi and University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy

    Rachele Ciccocioppo

  2. San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Alessio Cantore

  3. Vita Salute San Raffaele University, Milan, Italy

    Alessio Cantore

  4. Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Deborah Chaimov & Giuseppe Orlando

Authors
  1. Rachele Ciccocioppo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessio Cantore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deborah Chaimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Orlando
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rachele Ciccocioppo.

Ethics declarations

Conflict of interest

RC received a consulting (honorary) fee by Takeda Pharmaceuticals.

Statements on human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this study, formal consent was not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ciccocioppo, R., Cantore, A., Chaimov, D. et al. Regenerative medicine: the red planet for clinicians. Intern Emerg Med 14, 911–921 (2019). https://doi.org/10.1007/s11739-019-02126-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-019-02126-z

Keywords

Search

Navigation