Differential behavior of pericytes and adipose stromal cells in vasculogenesis and angiogenesis

Abstract

AbstractPerfusable vascularization of tissue-engineered systems remains one of the main hurdles in the field of providing large-scale functional tissues. Blood vessel formation by endothelial cells is dependent on supporting cells such as stromal cells. From them, the pericyte is the most relevant due to its close interaction with the endothelial cells, protecting them from external harm and architecting new vessels and connections. However, the identity of this cell type and its relation with other mesodermic cells, such as the mesenchymal stromal/stem cells, is highly debated. In this study, we delve on the distinct behavior of stromal cells and pericytes in the context of vascularization. The protein MCAM/CD146 was proposed as a specific marker for pericyte selection from adipose-derived stromal cells. By employing microfluidic chips that consist of an internal chamber flanked by two parallel media channels, we replicated the primary processes involved in vessel formation: vasculogenesis, which refers to the de novo vessel formation, and angiogenesis, the sprouting of new vessels from existing ones. In vasculogenesis, ASCs promoted the formation and proliferation of endothelial structures similar to the embryonic capillary plexus, whereas selected pericytes reduced their size and forced them to form vessel-like structures. In angiogenesis, on the other hand, pericytes promoted significantly more sprouting than the ASCs. Furthermore, this pericytic MCAM-enriched cell population exhibited an intimate interaction with endothelial cells leading to the synthesis of a shared basement membrane between these cell types, which was rarely observed for its unselected counterpart. These results shed light on the role of pericytes inin vitrovascularization and confirm the candidate marker MCAM/CD146 as a reliable marker for mural cell selection. In addition, the adipose pericyte is proposed as a very promising cell type to advance the field of tissue-engineered vascularization.