Angelini Francesco, Ionta Vittoria, Rossi Fabrizio, Miraldi Fabio, Messina Elisa, Giacomello Alessandro
Pasteur Institute - Cenci Bolognetti Foundation, "Sapienza" University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Department of Molecular Medicine, "Sapienza" University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Bioimpacts. 2016;6(1):15-24. doi: 10.15171/bi.2016.03. Epub 2016 Mar 28.
Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation.
The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells.
Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production.
These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures.
心脏祖细胞(CPCs)是心脏再生医学中的一种强大工具。临床前研究表明,注射细胞所带来的大多数有益效果归因于其对内源性细胞和组织发挥的旁分泌活性。外泌体是这种旁分泌效应的候选介质。鉴于其潜力,许多研究人员专注于对源自特定细胞类型的外泌体进行表征,但截至目前,仅有少数研究分析了牛血清来源的外泌体对细胞增殖或分化可能产生的体外效应。
本研究的目的是从定性和定量角度分析牛血清外泌体对以心脏球状体形式培养或以心脏球状体形成细胞单层形式培养的人CPCs的体外效应。
检测到了对增殖、产量和分子模式的影响。我们首次表明,外源性牛外泌体支持人心脏球状体形成细胞的增殖和迁移,并且其缺失会在大小、产量和细胞外基质产生方面影响心脏球状体的形成。
这些结果强调了考虑外源性细胞培养补充剂对原代人细胞培养最终表型的不同生物学效应的重要性。