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Paracrine potential of adipose stromal vascular fraction cells to recover hypoxia-induced loss of cardiomyocyte function MYTSYK et al.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Mytsyk Myroslava, Isu Giuseppe, Cerino Giulia, Grapow Martin T. R., Eckstein Friedrich S., Marsano Anna,
Project Engineered patches for cardiac repair
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Original article (peer-reviewed)

Journal Biotechnology and Bioengineering
Volume (Issue) 116(1)
Page(s) 132 - 142
Title of proceedings Biotechnology and Bioengineering
DOI 10.1002/bit.v116.1


Cell-based therapies show promising results in cardiac function recovery mostly through paracrine-mediated processes (as angiogenesis) in chronic ischemia. In this study, we aim to develop a 2D (two-dimensional) in vitro cardiac hypoxia model mimicking severe cardiac ischemia to specifically investigate the prosurvival paracrine effects of adipose tissue-derived stromal vascular fraction (SVF) cell secretome released upon three-dimensional (3D) culture. For the 2D-cardiac hypoxia model, neonatal rat cardiomyocytes (CM) were cultured for 5 days at < 1% (approaching anoxia) oxygen (O2 ) tension. Typical cardiac differentiation hallmarks and contractile ability were used to assess both the cardiomyocyte loss of functionality upon anoxia exposure and its possible recovery following the 5-day-treatment with SVF-conditioned media (collected following 6-day-perfusion-based culture on collagen scaffolds in either normoxia or approaching anoxia). The culture at < 1% O 2 for 5 days mimicked the reversible condition of hibernating myocardium with still living and poorly contractile CM (reversible state). Only SVF-medium conditioned in normoxia expressing a high level of the prosurvival hepatocyte-growth factor (HGF) and insulin-like growth factor (IGF) allowed the partial recovery of the functionality of damaged CM. The secretome generated by SVF-engineered tissues showed a high paracrine potential to rescue the nonfunctional CM, therefore resulting in a promising patch-based treatment of specific low-perfused areas after myocardial infarction.