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. 2020 Nov 16;9(11):2490. doi: 10.3390/cells9112490

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Cell-based therapies typically rely on isolating highly glycolytic stem cells from hypoxic niches followed by ex vivo expansion under high oxygen and glucose levels, which shifts energy generation towards a more oxidative metabolism. Upon transplantation, however, donated stem cells are exposed to an ischemic cardiac milieu characterized by an intense deprivation in oxygen and glucose essential for mitochondrial activity. This rough transition from in vitro to in vivo leads the cells to experience a metabolic stress driving transplanted cells towards apoptosis. Thus, the enhancement of stem cell metabolism holds a great promise towards promoting metabolic flexibility and improving cell survival and therapeutic efficacy.