Academic Journal
Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.
| Τίτλος: | Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation. |
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| Συγγραφείς: | Bhartiya D; TZAR Genomics India Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, Mumbai, 400013, India. deepa.bhartiya@tzarlabs.com., Sharma N; TZAR Genomics India Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, Mumbai, 400013, India., Tripathi A; Epigeneres Biotech Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, Mumbai, 400013, India., Tripathi A; TZAR Genomics India Pvt Ltd, Todi Mill Compound, Senapati Bapat Marg, Lower Parel, Mumbai, 400013, India.; 23Ikigai Pte Ltd, 137 Telok Ayer Street, Singapore, #05-02, 068602, Singapore. |
| Πηγή: | Stem cell reviews and reports [Stem Cell Rev Rep] 2026 Oct; Vol. 22 (7), pp. 3417-3438. Date of Electronic Publication: 2026 Jul 29. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Country of Publication: United States NLM ID: 101752767 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2629-3277 (Electronic) Linking ISSN: 26293277 NLM ISO Abbreviation: Stem Cell Rev Rep Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2011- : [New York, NY] : Springer Original Publication: [Totowa, N.J.] : Humana Press, [2009]- |
| Ιατρικοί όροι (MeSH): | Regenerative Medicine*/methods , Neoplasms*/therapy , Neoplasms*/pathology , Rejuvenation*/physiology , Cellular Reprogramming* , Cell Plasticity*, Induced Pluripotent Stem Cells/cytology ; Embryonic Stem Cells/cytology ; Humans ; Animals ; Cell Differentiation ; Cell Dedifferentiation |
| Περίληψη: | The successful culture of human embryonic stem (hES) cells from inner cell mass cells of blastocyst stage 'spare' embryos in 1998, followed by induced pluripotent stem (iPS) cells in 2006, which allowed somatic cells to be reprogrammed to pluripotency using the Yamanaka factors, transformed regenerative biology and inspired extensive global efforts towards developing pluripotent stem cell-based applications. However, hES and iPS cells, as well as organoids generated from them, largely retain fetal-like characteristics, which limits their relevance for clinical translation. Concurrently, the prevailing assumption published in leading journals that adult tissues lack endogenous stem cells has led to the belief that mature cells dedifferentiate and reprogram during in vivo regeneration upon chronic injury, and that the appearance of embryonic/fetal markers in diabetes, heart failure, cancer, and many other chronic disease states reflects dedifferentiation of mature cells. We suggest that the prevailing concepts of dedifferentiation and reprogramming, both in vitro and in vivo, require careful re-evaluation. Adult somatic cells possibly do not truly dedifferentiate, neither in vitro nor in vivo. Instead, tissue-resident, pluripotent, very small embryonic-like stem cells (VSELs) in multiple organs account for the observed biology. In vitro "reprogramming" responses to Yamanaka factors likely reflect selective activation and expansion of VSELs/early progenitors rather than the dedifferentiation/ reprogramming of mature adult somatic cells. Likewise, the embryonic/fetal-like signatures reported in multiple disease states including cancer reflect expansion of immature tissue-specific progenitors that arise from VSELs but fail to differentiate normally due to a damaged microenvironment in vivo. Therapeutic strategies involving transplantation of MSCs, MUSE cells, or their secreted exosomes improve disease outcomes, possibly by restoring the damaged niche that supports functional tissue repair by VSELs. Although direct evidence to support this is lacking at present, recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions. (© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethics approval: Not applicable. Clinical trial details: Not applicable. Consent to participate: Not applicable. Consent for publication: We have. Conflicts of interest: The author works at TZAR Genomics Pvt Ltd, with an interest in VSELs biology. |
| References: | Stem Cells. 2023 Apr 25;41(4):310-318. (PMID: 36881778) Front Endocrinol (Lausanne). 2024 Jun 10;15:1414447. (PMID: 38915897) Front Cell Dev Biol. 2025 Feb 18;13:1521411. (PMID: 40040790) Adv Exp Med Biol. 2018;1103:43-68. (PMID: 30484223) Life Sci. 2025 Dec 1;382:124024. (PMID: 41106719) Cells. 2023 Jun 21;12(13):. (PMID: 37443710) Leukemia. 2005 Jul;19(7):1118-27. (PMID: 15902288) Curr Top Med Chem. 2025;25(3):243-262. (PMID: 38797895) Int J Exp Pathol. 2005 Apr;86(2):67-79. (PMID: 15810978) BMC Med. 2018 Oct 2;16(1):166. (PMID: 30285732) Leukemia. 2010 Oct;24(10):1665-6. (PMID: 20940722) Oncotarget. 2024 Nov 22;15:793-805. (PMID: 39576660) Dev Cell. 2022 Feb 28;57(4):424-439. (PMID: 35231426) Nat Med. 2009 Oct;15(10):1145-8. (PMID: 19812575) EMBO Rep. 2010 May;11(5):353-9. (PMID: 20379220) Leukemia. 2024 Jun;38(6):1202-1212. (PMID: 38637690) Healthcare (Basel). 2025 Nov 17;13(22):. (PMID: 41302325) Stem Cell Rev Rep. 2026 May;22(4):2050-2060. (PMID: 41779358) J Adv Res. 2025 Apr;70:103-124. (PMID: 38729561) Leukemia. 2010 Aug;24(8):1450-61. (PMID: 20508611) J Clin Endocrinol Metab. 2025 May 19;110(6):e2096-e2097. (PMID: 39257186) Prog Retin Eye Res. 2026 Mar;111:101442. (PMID: 41577329) Circ Res. 2019 Mar 15;124(6):840-842. (PMID: 30870131) Front Oncol. 2015 Jul 20;5:155. (PMID: 26258068) Reprod Sci. 2021 Jan;28(1):278-290. (PMID: 32710237) Stem Cell Rev Rep. 2026 Apr;22(3):1051-1066. (PMID: 41644937) Cell. 2006 Aug 25;126(4):663-76. (PMID: 16904174) Mol Cells. 2010 Jun;29(6):533-8. (PMID: 20526817) Cell Death Dis. 2024 Apr 17;15(4):271. (PMID: 38632264) Science. 2025 May;388(6746):eadp2959. (PMID: 40310926) Int J Mol Sci. 2023 Nov 23;24(23):. (PMID: 38068992) Nat Cell Biol. 2001 Sep;3(9):778-84. (PMID: 11533656) Aging Cell. 2025 Nov;24(11):e70268. (PMID: 41114535) Stem Cell Rev Rep. 2024 May;20(4):857-880. (PMID: 38457060) Stem Cells Transl Med. 2017 Jun;6(6):1445-1451. (PMID: 28452204) Stem Cell Reports. 2019 Feb 12;12(2):305-318. (PMID: 30713040) Curr Res Toxicol. 2025 May 15;8:100238. (PMID: 40496982) Adv Exp Med Biol. 2018;1103:13-41. (PMID: 30484222) Exp Hematol. 2010 Dec;38(12):1131-1142.e1. (PMID: 20800644) J Clin Pathol. 2018 Jan;71(1):88-91. (PMID: 29180509) Cell. 2026 Feb 05;189(3):706-724. (PMID: 41650940) EMBO J. 2024 Jul;43(13):2530-2551. (PMID: 38773319) Regen Med. 2010 Jan;5(1):21-2. (PMID: 20017690) Nat Rev Genet. 2010 Sep;11(9):593. (PMID: 20717151) Front Immunol. 2024 Sep 25;15:1446687. (PMID: 39386216) Cell Stem Cell. 2025 Aug 7;32(8):1192-1199.e11. (PMID: 40744016) Cells. 2025 Jan 01;14(1):. (PMID: 39791735) Curr Biol. 2008 Jun 24;18(12):890-4. (PMID: 18501604) Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12172-9. (PMID: 23812749) Adv Exp Med Biol. 2018;1103:305-307. (PMID: 30484237) Diabetologia. 2025 Oct;68(10):2092-2103. (PMID: 40768044) Prog Cardiovasc Dis. 2025 Sep-Oct;92:66-79. (PMID: 40865707) Stem Cell Rev. 2008 Summer;4(2):81-8. (PMID: 18425605) Stem Cell Rev Rep. 2021 Apr;17(2):685-693. (PMID: 33492626) Stem Cell Rev Rep. 2020 Feb;16(1):181-185. (PMID: 31758373) Cell. 2005 May 6;121(3):465-77. (PMID: 15882627) Nat Med. 2025 Feb;31(2):409-421. (PMID: 39901045) Nature. 2025 Jan;637(8044):18-20. (PMID: 39707007) Stem Cell Rev Rep. 2021 Oct;17(5):1695-1711. (PMID: 34455541) Blood. 2009 May 28;113(22):5476-9. (PMID: 19299331) EMBO Rep. 2014 Mar;15(3):244-53. (PMID: 24531722) J Ovarian Res. 2018 Sep 21;11(1):83. (PMID: 30241552) Blood Rev. 2024 Nov;68:101226. (PMID: 39164126) Cell Death Discov. 2017 Jan 23;3:16105. (PMID: 28179999) Stem Cell Rev Rep. 2025 Jun;21(5):1471-1483. (PMID: 40238074) Cell Mol Life Sci. 2012 Nov;69(22):3739-50. (PMID: 22527723) Front Cell Dev Biol. 2026 Apr 30;14:1824475. (PMID: 42148296) Stem Cell Rev Rep. 2018 Oct;14(5):715-721. (PMID: 29876729) Cell Stem Cell. 2021 Nov 4;28(11):2009-2019.e4. (PMID: 34358441) Leukemia. 2006 May;20(5):857-69. (PMID: 16498386) Cell Rep. 2017 Feb 21;18(8):1930-1945. (PMID: 28228259) J Ovarian Res. 2016 Mar 03;9:12. (PMID: 26940129) Front Bioeng Biotechnol. 2025 Mar 07;13:1564964. (PMID: 40124247) Nat Rev Cancer. 2019 Dec;19(12):716-732. (PMID: 31666716) Int J Mol Sci. 2025 Mar 27;26(7):. (PMID: 40243729) Philos Trans R Soc Lond B Biol Sci. 2013 Jan 5;368(1609):20120292. (PMID: 23166402) Mol Biomed. 2025 Jun 4;6(1):34. (PMID: 40465163) J Ovarian Res. 2021 Oct 30;14(1):145. (PMID: 34717703) Diabetes. 2025 Jul 1;74(7):1068-1077. (PMID: 40272266) Nat Chem Biol. 2025 Jul;21(7):1030-1038. (PMID: 39753706) Stem Cell Rev Rep. 2016 Dec;12(6):682-697. (PMID: 27663915) Nat Rev Cardiol. 2025 May;22(5):372-385. (PMID: 39548233) Stem Cell Rev Rep. 2017 Apr;13(2):202-216. (PMID: 28070859) Stem Cell Rev Rep. 2020 Feb;16(1):144-158. (PMID: 31705263) Cell Death Dis. 2025 Feb 19;16(1):113. (PMID: 39971901) Stem Cell Rev Rep. 2022 Dec;18(8):3112-3114. (PMID: 35829891) Leukemia. 2017 Aug;31(8):1671-1677. (PMID: 28502982) Aging (Albany NY). 2011 Jul;3(7):692-7. (PMID: 21765200) Science. 2008 Aug 1;321(5889):699-702. (PMID: 18276851) Front Cell Dev Biol. 2023 Jan 04;10:1061022. (PMID: 36684436) Cytotherapy. 2025 Jul;27(7):835-842. (PMID: 39969437) Biochem Biophys Res Commun. 2004 Apr 9;316(3):651-8. (PMID: 15033449) Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9875-80. (PMID: 21628574) Reproduction. 2023 Jan 18;165(3):249-268. (PMID: 36488194) Trends Biochem Sci. 2025 Jun;50(6):520-531. (PMID: 40169299) Nat Biotechnol. 2019 Mar;37(3):232-237. (PMID: 30778231) Bioeng Transl Med. 2025 Feb 04;10(3):e70000. (PMID: 40385529) Annu Rev Physiol. 2022 Feb 10;84:461-483. (PMID: 34705482) Trends Cell Biol. 2024 Mar;34(3):255-267. (PMID: 37648593) Cell. 2012 Sep 14;150(6):1223-34. (PMID: 22980982) Science. 2013 Aug 9;341(6146):651-4. (PMID: 23868920) Front Cell Dev Biol. 2025 Apr 28;13:1587893. (PMID: 40356600) Cell. 2024 Jun 20;187(13):3229-3230. (PMID: 38906098) Stem Cell Rev Rep. 2023 Oct;19(7):2525-2540. (PMID: 37561284) Stem Cell Rev Rep. 2020 Oct;16(5):992-1004. (PMID: 32578128) Genomics Proteomics Bioinformatics. 2013 Oct;11(5):304-11. (PMID: 24080286) Stem Cell Rev Rep. 2022 Jun;18(5):1702-1717. (PMID: 35389139) Cell. 2024 Dec 26;187(26):7394-7413.e22. (PMID: 39626658) J Diabetes Investig. 2013 Jul 8;4(4):331-3. (PMID: 24843674) Diabetes Res Clin Pract. 2022 Jan;183:109119. (PMID: 34879977) Clin Chem Lab Med. 2019 Mar 26;57(4):403-406. (PMID: 30530899) Stem Cell Rev Rep. 2026 May;22(4):2029-2032. (PMID: 41758309) Hum Reprod Update. 2016 Dec;23(1):41-76. (PMID: 27614362) Inflamm Regen. 2020 May 12;40:8. (PMID: 32426078) Cell Prolif. 2008 Feb;41 Suppl 1:51-6. (PMID: 18181945) Stem Cell Rev Rep. 2024 Jan;20(1):258-282. (PMID: 37779174) Nat Cell Biol. 2024 Feb;26(2):171. (PMID: 38307997) ESMO Open. 2025 Sep;10(9):105553. (PMID: 40907212) Circulation. 2024 Jul 30;150(5):347-349. (PMID: 39074179) Vet Pathol. 2009 Mar;46(2):176-93. (PMID: 19261629) Circ Res. 2017 Jan 6;120(1):166-178. (PMID: 28057792) Adv Exp Med Biol. 2025;1474:149-177. (PMID: 39470980) Kardiol Pol. 2025;83(4):417-426. (PMID: 40066964) Stem Cell Rev Rep. 2018 Aug;14(4):510-524. (PMID: 29736843) J Am Heart Assoc. 2025 Jul;14(13):e038644. (PMID: 40557798) Stem Cells Transl Med. 2014 Oct;3(10):1182-7. (PMID: 25122691) Cell. 2008 Apr 18;133(2):250-64. (PMID: 18423197) Adv Exp Med Biol. 2018;1103:115-129. (PMID: 30484226) Mol Ther. 2025 Jun 4;33(6):2679-2688. (PMID: 39916329) Stem Cell Rev Rep. 2017 Dec;13(6):713-724. (PMID: 28815441) Exp Cell Res. 2010 Oct 1;316(16):2565-70. (PMID: 20420827) Hum Reprod Update. 2021 Feb 19;27(2):421. (PMID: 33367724) Regen Med. 2026 Mar-Apr;21(3-4):281-290. (PMID: 42026853) Leukemia. 2018 Dec;32(12):2519-2526. (PMID: 30375490) Nature. 2013 Oct 17;502(7471):340-5. (PMID: 24025773) Nature. 2010 Sep 16;467(7313):285-90. (PMID: 20644535) Nat Commun. 2024 Mar 2;15(1):1941. (PMID: 38431638) Leukemia. 2015 Sep;29(9):1909-17. (PMID: 25882698) Stem Cells. 2005 Jun-Jul;23(6):727-37. (PMID: 15917469) Cell Stem Cell. 2010 Jul 2;7(1):11-4. (PMID: 20621043) Circ Res. 2019 Jan 18;124(2):208-210. (PMID: 30653438) Nat Commun. 2025 Oct 7;16(1):8434. (PMID: 41057332) J Clin Endocrinol Metab. 2016 Mar;101(3):1044-54. (PMID: 26713822) Nat Biotechnol. 2010 Aug;28(8):848-55. (PMID: 20644536) Signal Transduct Target Ther. 2025 Aug 22;10(1):262. (PMID: 40841367) Cell Stem Cell. 2010 Jul 2;7(1):15-9. (PMID: 20621044) Dis Model Mech. 2026 Jun 1;19(6):. (PMID: 41854394) |
| Contributed Indexing: | Keywords: Dedifferentiation; MSCs; Regeneration; Reprogramming; VSELs; iPS cells |
| Entry Date(s): | Date Created: 20260729 Date Completed: 20260907 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s12015-026-11197-3 |
| PMID: | 42527762 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2629-3277 |
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| DOI: | 10.1007/s12015-026-11197-3 |