The Matrix Protein Tropoelastin Prolongs Mesenchymal Stromal Cell Vitality and Delays Senescence During Replicative Aging.

Autor: Lee SS; School of Life & Environmental Sciences and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia., Al Halawani A; School of Life & Environmental Sciences and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia., Teo JD; School of Medical Sciences and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia., Weiss AS; School of Life & Environmental Sciences and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia.; Sydney Nano Institute, The University of Sydney, Camperdown, NSW, 2006, Australia., Yeo GC; School of Life & Environmental Sciences and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia.; Sydney Nano Institute, The University of Sydney, Camperdown, NSW, 2006, Australia.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Oct; Vol. 11 (39), pp. e2402168. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1002/advs.202402168
Abstrakt: Cellular senescence leads to the functional decline of regenerative cells such as mesenchymal stromal/stem cells (MSCs), which gives rise to chronic conditions and contributes to poor cell therapy outcomes. Aging tissues are associated with extracellular matrix (ECM) dysregulation, including loss of elastin. However, the role of the ECM in modulating senescence is underexplored. In this work, it is shown that tropoelastin, the soluble elastin precursor, is not only a marker of young MSCs but also actively preserves cell fitness and delays senescence during replicative aging. MSCs briefly exposed to tropoelastin exhibit upregulation of proliferative genes and concurrent downregulation of senescence genes. The seno-protective benefits of tropoelastin persist during continuous, long-term MSC culture, and significantly extend the MSC replicative lifespan. Tropoelastin-expanded MSCs further maintain youth-associated phenotype and function compared to age-matched controls, including preserved clonogenic potential, minimal senescence-associated beta-galactosidase activity, maintained cell sizes, reduced expression of senescence markers, suppressed secretion of senescence-associated factors, and increased production of youth-associated proteins. This work points to the utility of exogenously-supplemented tropoelastin for manufacturing MSCs that robustly maintain regenerative potential with age. It further reveals the active role of classical structural ECM proteins in driving cellular age-associated fitness, potentially leading to future interventions for aging-related pathologies.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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