A Metabolic Signature to Monitor Endothelial Cell Differentiation, Activation, and Vascular Organization

Biomedicines. 2022 Sep 15;10(9):2293. doi: 10.3390/biomedicines10092293.

Abstract

The formation of new blood vessels is an important step in the morphogenesis and organization of tissues and organs; hence, the success of regenerative medicine procedures is highly dependent on angiogenesis control. Despite the biotechnological advances, tissue engineering is still a challenge. Regarding vascular network formation, the regulators are well known, yet the identification of markers is pivotal in order to improve the monitoring of the differentiation and proliferation of endothelial cells, as well as the establishment of a vascular network supporting tissue viability for an efficacious implantation. The metabolic profile accompanies the physiological stages of cells involved in angiogenesis, being a fruitful hub of biomarkers, whose levels can be easily retrieved. Through NMR spectroscopy, we identified branched amino acids, acetate, and formate as central biomarkers of monocyte-to-endothelial-cell differentiation and endothelial cell proliferation. This study reinforces the successful differentiation process of monocytes into endothelial cells, allowing self-to-self transplantation of patient-derived vascular networks, which is an important step in tissue engineering, since monocytes are easily isolated and autologous transplantation reduces the immune rejection events.

Keywords: biomarkers; differentiation; endothelial cells; metabolic profile; metabolic signature; monocytes; sprouting.

Grants and funding

The institutions are funded by Fundação para a Ciência e Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020), and the Associated Laboratory LS4FUTURE (LA/P/0087/2020). Filipa Lopes-Coelho’s fellowship was funded by FCT (PD/BD/128337/2017). Luis G. Gonçalves was financed by an FCT contract according to DL57/2016 (SFRH/BPD/111100/2015). This work benefited from access to CERMAX, ITQB NOVA, Oeiras, Portugal, with equipment funded by FCT, project AAC 01/SAICT/2016.