Reprogramming iPSCs to study age-related diseases: Models, therapeutics, and clinical trials

Filipa Esteves; David Brito; Ana Teresa Rajado; Nádia Silva; Joana Apolónio; Vânia Palma Roberto; Inês Araújo; Clévio Nóbrega; Pedro Castelo-Branco; José Bragança; ALFA Score Consortium

doi:10.1016/j.mad.2023.111854

Reprogramming iPSCs to study age-related diseases: Models, therapeutics, and clinical trials

Mech Ageing Dev. 2023 Sep:214:111854. doi: 10.1016/j.mad.2023.111854. Epub 2023 Aug 12.

Collaborators

ALFA Score Consortium:
Raquel P Andrade⁵, Sofia Calado⁶, Maria Leonor Faleiro⁷, Carlos Matos⁶, Nuno Marques⁸, Ana Marreiros⁸, Hipólito Nzwalo⁸, Sandra Pais⁸, Isabel Palmeirim⁹, Sónia Simão⁸, Natércia Joaquim¹⁰, Rui Miranda¹⁰, António Pêgas¹¹, Daniela Marques Raposo¹², Ana Sardo¹²

Affiliations

¹ Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal.
² Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; ABC Collaborative Laboratory, Association for Integrated Aging and Rejuvenation Solutions (ABC CoLAB), 8100-735 Loulé, Portugal.
³ Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; ABC Collaborative Laboratory, Association for Integrated Aging and Rejuvenation Solutions (ABC CoLAB), 8100-735 Loulé, Portugal; Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Champalimaud Research Program, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal.
⁴ Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; ABC Collaborative Laboratory, Association for Integrated Aging and Rejuvenation Solutions (ABC CoLAB), 8100-735 Loulé, Portugal; Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Champalimaud Research Program, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal. Electronic address: jebraganca@ualg.pt.
⁵ Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Champalimaud Research Program, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal; ABC Collaborative Laboratory, Association for Integrated Aging and Rejuvenation Solutions (ABC CoLAB), 8100-735 Loulé, Portugal.
⁶ Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal.
⁷ Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; Faculty of Science and Technology (FCT), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal.
⁸ Champalimaud Research Program, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal; Faculty of Science and Technology (FCT), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; USF Ossónoba, 8009-003 Faro, Portugal.
⁹ Champalimaud Research Program, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal; Faculty of Science and Technology (FCT), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal; USF Ossónoba, 8009-003 Faro, Portugal; USF Mirante, 8700-240 Olhão, Portugal.
¹⁰ USF Balsa, 8800-534 Tavira, Portugal.
¹¹ USF Ossónoba, 8009-003 Faro, Portugal.
¹² USF Mirante, 8700-240 Olhão, Portugal.

PMID: 37579530
DOI: 10.1016/j.mad.2023.111854

Abstract

The unprecedented rise in life expectancy observed in the last decades is leading to a global increase in the ageing population, and age-associated diseases became an increasing societal, economic, and medical burden. This has boosted major efforts in the scientific and medical research communities to develop and improve therapies to delay ageing and age-associated functional decline and diseases, and to expand health span. The establishment of induced pluripotent stem cells (iPSCs) by reprogramming human somatic cells has revolutionised the modelling and understanding of human diseases. iPSCs have a major advantage relative to other human pluripotent stem cells as their obtention does not require the destruction of embryos like embryonic stem cells do, and do not have a limited proliferation or differentiation potential as adult stem cells. Besides, iPSCs can be generated from somatic cells from healthy individuals or patients, which makes iPSC technology a promising approach to model and decipher the mechanisms underlying the ageing process and age-associated diseases, study drug effects, and develop new therapeutic approaches. This review discusses the advances made in the last decade using iPSC technology to study the most common age-associated diseases, including age-related macular degeneration (AMD), neurodegenerative and cardiovascular diseases, brain stroke, cancer, diabetes, and osteoarthritis.

Keywords: Age-related diseases; Disease modelling; IPSC; Mechanisms; Therapeutics.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adult Stem Cells*
Aging
Cell Differentiation
Humans
Induced Pluripotent Stem Cells*
Pluripotent Stem Cells*