Cellular therapy for chronic heart failure: a key role for epicardial fibronectin
| Autor: | Ong, Lay Ping |
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| Rok vydání: | 2022 |
| Předmět: | |
| DOI: | 10.17863/cam.80910 |
| Popis: | Myocardial infarction (MI) results in permanent cardiomyocyte loss, frequently leading to heart failure, with a 50% 5-year mortality. At subacute time points following MI, animal studies have shown ‘remuscularization’ of the damaged heart with human embryonic stem cell (hESC)-derived cardiomyocytes. Recently, outcomes were improved by co-delivering hESC-derived epicardium. Clinically, the main challenge remains chronic heart failure. However, hESC-cardiomyocytes alone, in the chronically infarcted heart, have shown no benefit. Here, we show that both species-matched cellular therapy and combination therapy with hESC-epicardium could attenuate cardiac dysfunction in the chronically failing heart, underpinned by sizeable cardiac grafts, cardiomyocyte proliferation and maturation, together with a host-derived vascular supply. Notably, hESC-epicardium’s augmentation of cardiomyocyte maturation within 3D-engineered heart tissues in vitro appeared to be underpinned by epicardial-secreted fibronectin. Thus, hESC-combination cell therapy holds clinical promise for ‘remuscularising’ chronically infarcted hearts. Wellcome Trust, Addenbrooke's Charitable Trust |
| Databáze: | OpenAIRE |
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