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Impact of Diabetes Mellitus on the Potential of Autologous Stem Cells and Stem Cell–Derived Microvesicles to Repair the Ischemic Heart

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Abstract

Ischemic heart disease remains the leading cause of morbidity and mortality worldwide. Despite the advances in medical management and catheter-based therapy, mortality remains high, as does the risk of developing heart failure. Regenerative therapies have been widely used as an alternative option to repair the damaged heart mainly because of their paracrine-related beneficial effects. Although cell-based therapy has been demonstrated as feasible and safe, randomized controlled trials and meta-analyses show little consistent benefit from treatments with adult-derived stem cells. Mounting evidence from our group and others supports that cardiovascular risk factors and comorbidities impair stem cell potential thus hampering their autologous use. This review aims to better understand the influence of diabetes on stem cell potential. For this purpose, we will first discuss the most recent advances in the mechanistic understanding of the effects of diabetes on stem cell phenotype, function, and molecular fingerprint to further elaborate on diabetes-induced alterations in stem cell extracellular vesicle profile. Although we acknowledge that multiple sources of stem or progenitor cells are used for regenerative purposes, we will focus on bone marrow hematopoietic stem/progenitor cells, mesenchymal stem cells residing in the bone marrow, and adipose tissue and briefly discuss endothelial colony-forming cells.

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Funding

LB has been funded by PID2019-107160RB-I00 from the Spanish Ministry of Science and Innovation and FEDER “Una Manera de Hacer Europa,” Red TerCel (Terapia Celular) RD16/0011/0018 , and CIBERCV from Carlos III Institute and European Union-H2020 grants. GV is funded by PGC2018-094025-B-I00 from Spanish Ministry of Science and Innovation and FEDER “Una Manera de Hacer Europa”. LB and GV thank the support of the Generalitat of Catalunya (Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat, 2017 SGR 1480) and the Fundación Investigación Cardiovascular-Fundación Jesus Serra for their continuous support.

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  1. Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, C/Sant Antoni Mª Claret 167, 08025, Barcelona, Spain

    Gemma Vilahur, Phuong Hue Nguyen & Lina Badimon

  2. Ciber CV - ISCIII, Madrid, Spain

    Gemma Vilahur & Lina Badimon

  3. Cardiovascular Research Chair UAB, Barcelona, Spain

    Lina Badimon

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  1. Gemma Vilahur
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  2. Phuong Hue Nguyen
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  3. Lina Badimon
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GV wrote the review; PHN contributed to the writing of the review and the figures; LB revised and corrected the entire review.

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Correspondence to Lina Badimon.

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LB declares to have acted as SAB member of Sanofi, Bayer, AstraZeneca, and the International Aspirin Foundation; has a research grant from AstraZeneca, speaker fees from Lilly, MSD-Boerhinger, and AstraZeneca; and to have founded the Spin-offs Glycardial Diagnostics SL. and IVESTATIN Therapeutics SL. (all outside of the area of the present work). GV has a research grant from AstraZeneca and is founder of the Spin-offs Glycardial Diagnostics SL. and IVESTATIN Therapeutics SL. (all outside of the area of the present work).

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Vilahur, G., Nguyen, P.H. & Badimon, L. Impact of Diabetes Mellitus on the Potential of Autologous Stem Cells and Stem Cell–Derived Microvesicles to Repair the Ischemic Heart. Cardiovasc Drugs Ther 36, 933–949 (2022). https://doi.org/10.1007/s10557-021-07208-9

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