Academic Journal

Deciphering reprogramming efficiency in human induced pluripotent stem cells: insights from the generation of 150 cell lines.

Bibliographic Details
Title: Deciphering reprogramming efficiency in human induced pluripotent stem cells: insights from the generation of 150 cell lines.
Authors: Kuebler B; Barcelona Stem Cell Bank, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L´Hospitalet de Llobregat, Spain.; Program for Clinical Translation of Regenerative Medicine in Catalonia (P-[CMRC]), L´Hospitalet de Llobregat, Spain., Selvitella S; Barcelona Stem Cell Bank, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L´Hospitalet de Llobregat, Spain.; Program for Clinical Translation of Regenerative Medicine in Catalonia (P-[CMRC]), L´Hospitalet de Llobregat, Spain., Aran B; Barcelona Stem Cell Bank, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L´Hospitalet de Llobregat, Spain.; Program for Clinical Translation of Regenerative Medicine in Catalonia (P-[CMRC]), L´Hospitalet de Llobregat, Spain., Raya A; Program for Clinical Translation of Regenerative Medicine in Catalonia (P-[CMRC]), L´Hospitalet de Llobregat, Spain.; Stem Cell Potency Group, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L´Hospitalet de Llobregat, Spain.; Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.; Physiological Sciences Department, Faculty of Medicine and Health Sciences, University of Barcelona, L´Hospitalet de Llobregat, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., Veiga A; Barcelona Stem Cell Bank, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L´Hospitalet de Llobregat, Spain.; Program for Clinical Translation of Regenerative Medicine in Catalonia (P-[CMRC]), L´Hospitalet de Llobregat, Spain.
Source: Frontiers in immunology [Front Immunol] 2026 Jan 13; Vol. 16, pp. 1719056. Date of Electronic Publication: 2026 Jan 13 (Print Publication: 2025).
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
MeSH Terms: Induced Pluripotent Stem Cells*/cytology , Induced Pluripotent Stem Cells*/metabolism , Induced Pluripotent Stem Cells*/physiology , Cellular Reprogramming*/genetics, Humans ; Cell Line ; Cell Differentiation ; Cellular Reprogramming Techniques
Abstract: Introduction: The discovery of induced pluripotent stem cells (iPSCs) revolutionized the field of translational medicine by enabling the reprogramming of adult somatic cells into a pluripotent state. From personalized disease models to innovative cell therapies, iPSCs are poised to play a central role in the future of clinical medicine. iPSCs hold enormous promises due to their ability to self-renew indefinitely and differentiate into all somatic cell types, thus offering patient-specific cellular models and therapeutic options without the ethical constraints of embryonic stem cells (ESCs). iPSCs, which exhibit pluripotency similar to embryonic stem cells, are generated by introducing specific factors into terminally differentiated cells, inducing a shift in their epigenetic and transcriptional landscape, which leads to the reactivation of the pluripotency program of the cells. Nevertheless, the mechanisms underlying successful reprogramming remain poorly understood.
Methods: In this study we performed a statistical evaluation of reprogramming efficiencies of 150 iPSC lines generated in our lab, comparing factors such as the starting somatic cell type, passage number, donor´s health status, donor age and sex, reprogramming methodology, and growth conditions.
Results/discussion: We found that the most relevant factor influencing reprogramming efficiency is the developmental status of the starting cells. While other parameters may exert minor effects, inherent donor-specific biological characteristics appear to play the strongest role in determining reprogramming outcomes.
(Copyright © 2026 Kuebler, Selvitella, Aran, Raya and Veiga.)
Competing Interests: The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
References: Aging Cell. 2019 Feb;18(1):e12877. (PMID: 30450724)
Stem Cells Int. 2025 Jan 16;2025:2223645. (PMID: 39850337)
Stem Cell Res. 2015 Jul;15(1):254-62. (PMID: 26096152)
Cell Stem Cell. 2013 Aug 1;13(2):246-54. (PMID: 23910086)
Stem Cell Res. 2020 Dec;49:102092. (PMID: 33254092)
Nat Biotechnol. 2015 Jan;33(1):58-63. (PMID: 25437882)
Cell. 2007 Nov 30;131(5):861-72. (PMID: 18035408)
Nat Methods. 2011 May;8(5):409-12. (PMID: 21460823)
Science. 2007 Dec 21;318(5858):1917-20. (PMID: 18029452)
Nat Protoc. 2011 Jan;6(1):78-88. (PMID: 21212777)
Nature. 2009 Apr 9;458(7239):766-70. (PMID: 19252478)
Cell Rep Methods. 2022 Oct 17;2(11):100317. (PMID: 36447645)
Front Cell Dev Biol. 2024 Jan 11;11:1328522. (PMID: 38274274)
Int J Mol Med. 2024 Dec;54(6):. (PMID: 39422061)
Cell. 2006 Aug 25;126(4):663-76. (PMID: 16904174)
PLoS One. 2015 Jul 01;10(7):e0131128. (PMID: 26131765)
Methods Mol Biol. 2013;997:45-56. (PMID: 23546747)
Science. 2009 May 8;324(5928):797-801. (PMID: 19325077)
Curr Opin Cell Biol. 2012 Dec;24(6):744-56. (PMID: 23146768)
Stem Cell Res Ther. 2023 Dec 13;14(1):366. (PMID: 38093328)
Stem Cells. 2009 Nov;27(11):2667-74. (PMID: 19697349)
Stem Cell Rev Rep. 2021 Dec;17(6):1954-1974. (PMID: 34100193)
Front Cell Dev Biol. 2025 May 08;13:1593207. (PMID: 40406420)
Stem Cell Rev Rep. 2016 Feb;12(1):54-72. (PMID: 26424535)
Stem Cell Reports. 2014 Sep 9;3(3):414-22. (PMID: 25241740)
Stem Cells Dev. 2025 Aug;34(15-16):317-332. (PMID: 40601490)
Development. 2024 Oct 1;151(19):. (PMID: 39348466)
Cell. 2012 Oct 26;151(3):547-58. (PMID: 23101625)
Cell Stem Cell. 2011 Jun 3;8(6):633-8. (PMID: 21620789)
Signal Transduct Target Ther. 2024 Apr 26;9(1):112. (PMID: 38670977)
Nat Protoc. 2013 Mar;8(3):568-82. (PMID: 23429718)
Nat Biotechnol. 2009 May;27(5):459-61. (PMID: 19363475)
Sci Adv. 2020 Nov 20;6(47):. (PMID: 33219026)
Nat Chem Biol. 2025 Jul;21(7):1030-1038. (PMID: 39753706)
Nat Commun. 2018 Jul 06;9(1):2643. (PMID: 29980666)
Cells. 2021 Jun 11;10(6):. (PMID: 34208270)
Cell Stem Cell. 2009 Jun 5;4(6):472-6. (PMID: 19481515)
Stem Cell Res. 2017 Dec;25:1-5. (PMID: 29246570)
Comput Biol Med. 2024 Jul;177:108661. (PMID: 38810477)
Stem Cells Dev. 2013 Feb 15;22(4):595-610. (PMID: 22931452)
Nat Protoc. 2010 Apr;5(4):811-20. (PMID: 20360773)
Front Cardiovasc Med. 2018 Jan 25;5:4. (PMID: 29423397)
Stem Cell Res. 2020 Dec;49:102087. (PMID: 33370870)
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19467-72. (PMID: 20974949)
Stem Cell Rev Rep. 2015 Dec;11(6):900-8. (PMID: 26341105)
Nat Biomed Eng. 2017 Oct;1(10):826-837. (PMID: 30263871)
Science. 2013 Aug 9;341(6146):651-4. (PMID: 23868920)
Cell Stem Cell. 2009 May 8;4(5):381-4. (PMID: 19398399)
Front Cell Dev Biol. 2023 Jan 17;10:1050856. (PMID: 36733338)
Stem Cell Res Ther. 2012 Aug 03;3(4):30. (PMID: 22862934)
Mol Ther. 2012 Feb;20(2):408-16. (PMID: 22108860)
Science. 2008 Nov 7;322(5903):945-9. (PMID: 18818365)
Eur J Pharmacol. 2025 Sep 15;1003:177786. (PMID: 40513933)
Aging Cell. 2016 Feb;15(1):56-66. (PMID: 26637971)
Stem Cell Res. 2024 Dec;81:103606. (PMID: 39541769)
Stem Cells. 2018 Nov;36(11):1697-1708. (PMID: 30152570)
Adv Exp Med Biol. 2025;1486:321-327. (PMID: 41136850)
Cytotherapy. 2024 Nov;26(11):1275-1284. (PMID: 38970614)
Nat Biotechnol. 2011 Nov 27;29(12):1117-9. (PMID: 22119740)
Nature. 2022 May;605(7909):325-331. (PMID: 35418683)
Cell Stem Cell. 2010 Nov 5;7(5):618-30. (PMID: 20888316)
Stem Cell Reports. 2023 Sep 12;18(9):1744-1752. (PMID: 37703820)
Biomater Res. 2023 Jul 7;27(1):67. (PMID: 37420273)
Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14234-9. (PMID: 21821793)
Cell Stem Cell. 2011 Apr 8;8(4):376-88. (PMID: 21474102)
Stem Cell Reports. 2022 Feb 8;17(2):413-426. (PMID: 35063129)
Stem Cell Res. 2017 Dec;25:291-295. (PMID: 29150092)
Nature. 2009 Apr 9;458(7239):771-5. (PMID: 19252477)
Cell Stem Cell. 2023 Apr 6;30(4):450-459.e9. (PMID: 36944335)
Nat Commun. 2018 Feb 21;9(1):745. (PMID: 29467427)
Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(8):348-62. (PMID: 19838014)
Science. 2016 Nov 25;354(6315):. (PMID: 27884981)
Nat Protoc. 2013 Feb;8(2):223-53. (PMID: 23306458)
Contributed Indexing: Keywords: iPSC characterization; induced pluripotent stem cells; integrating reprogramming methods; non-integrating reprogramming methods; reprogramming efficiency
Entry Date(s): Date Created: 20260129 Date Completed: 20260701 Latest Revision: 20260701
Update Code: 20260701
PubMed Central ID: PMC12834790
DOI: 10.3389/fimmu.2025.1719056
PMID: 41607802
Database: MEDLINE
Description
ISSN:1664-3224
DOI:10.3389/fimmu.2025.1719056