Abstract
Adipose-derived mesenchymal stem/stromal cells (ASCs) are an adult stem cell population able to self-renew and differentiate into numerous cell lineages. ASCs provide a promising future for therapeutic angiogenesis due to their ability to promote blood vessel formation. Specifically, their ability to differentiate into endothelial cells (ECs) and pericyte-like cells and to secrete angiogenesis-promoting growth factors and extracellular vesicles (EVs) makes them an ideal option in cell therapy and in regenerative medicine in conditions including tissue ischemia. In recent angiogenesis research, ASCs have often been co-cultured with an endothelial cell (EC) type in order to form mature vessel-like networks in specific culture conditions. In this review, we introduce co-culture systems and co-transplantation studies between ASCs and ECs. In co-cultures, the cells communicate via direct cell–cell contact or via paracrine signaling. Most often, ASCs are found in the perivascular niche lining the vessels, where they stabilize the vascular structures and express common pericyte surface proteins. In co-cultures, ASCs modulate endothelial cells and induce angiogenesis by promoting tube formation, partly via secretion of EVs. In vivo co-transplantation of ASCs and ECs showed improved formation of functional vessels over a single cell type transplantation. Adipose tissue as a cell source for both mesenchymal stem cells and ECs for co-transplantation serves as a prominent option for therapeutic angiogenesis and blood perfusion in vivo.
Highlights
Endothelial dysfunction is known to be a common denominator of various pathophysiological conditions such as diabetes mellitus, coronary heart disease and stroke [1,2,3].Endothelial dysfunction results in ischemia in the nearby tissues, impairing cellular regeneration mechanisms, which can eventually lead to tissue necrosis
These findings suggest that hASCs show a more prominent pericyte phenoA comparison of human umbilical vein endothelial cells (HUVECs)/hASC and HUVEC/bone marrow-derived stem/stromal cells stem/stromal (BM-MSCs) co-cultures demonstrated type in a 3D environment compared with a standard monolayer culture
Ma et al [76] showed that HUVEC/BM-MSC and HUVEC/hASC co-cultures have an equal ability to induce angiogenesis in collagen, which was not the case in monocultures, suggesting that a supporting cell type and direct contact are essential in network formation and stabilization, possibly through paracrine factors secreted by the hASCs
Summary
Endothelial dysfunction is known to be a common denominator of various pathophysiological conditions such as diabetes mellitus, coronary heart disease and stroke [1,2,3]. Adipose-derived mesenchymal stem/stromal cells (ASCs) provide a promising option to treat endothelial dysfunction since they can promote angiogenesis through growth factor and extracellular vesicle production and differentiate into either endothelial cells or pericyte-like cells [4,5,6]. Due to these favorable characteristics, and because they are easy to harvest, ASCs are a potential option for cell therapies. Current research aims to develop methods that can aid the tissue regeneration process in ischemic conditions via the administration of healthy, pro-angiogenic stem cells or their extracellular vesicles either directly or in a vascular graft. As a novel possibility for therapeutic purposes, ASC-derived extracellular vesicles and their angiogenesis-promoting qualities and cellular mechanisms will be discussed
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