Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells

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.

Guiding cell migration in 3D with high-resolution photografting

“…A large number of publications are focusing on the interplay of ASCs and HUVECs. A good overview is given in the review paper by Rautiainen et al (2021), which highlights the importance of direct contact between ECs and ASCs for endothelial network formation 78 . Based on these publications, it seems like hASCs are supporting HUVEC migration by providing chemical cues and by creating degraded pathways within the hydrogel.…”

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

“…Special attention is paid to the angiogenic effects of ASC-derived EVs [51]. Proangiogenic effects could be ascribed to the presence of some miRNAs including miR-31, miR-125 and miR-126.…”

“…[33] EVs, similar to iPSCs and unlike MSCs, should not be tumorigenic and, in selected cases, could also serve as a new anticancer tool [103][104][105] Data are still conflicting. One should not forget the angiogenic properties of EVs, which may favor tumor growth/expansion or the development/worsening of metabolic diseases [51,[105][106][107] Abbreviations: ASCs, adipose stromal/stem cells; BBB: blood-brain barrier; EVs, extracellular vesicles; iPSCs, induced pluripotent stem cells; MSCs, mesenchymal stem cells, SAT, subcutaneous adipose tissue.…”

“…Finally, it should be noted that obesity severely modifies the properties of EVs, enhancing their inflammatory profile [49] as well as the activity of HIFs contained in ASC-derived EVs [51], which could also promote metabolic diseases, as observed in diet-induced disease models [107]. Thus, biotechnological modification of the EVs aimed at eliminating these factors could be useful for the treatment of those disorders.…”

Molecular Morphology and Function of Stromal Cells

“…A comprehensive review written by Rautiainen et al [7] is dedicated to the angiogenic effects and crosstalk of ASCs and their extracellular vesicles with endothelial cells. Focusing on different co-culture systems and co-transplantation studies between ASCs and endothelial cells, the authors review the state-of-the-art evidence for the ability of ASCs to differentiate into endothelial cells and pericyte-like cells and to secrete angiogenesispromoting growth factors and extracellular vesicles, which makes them an ideal option in cell therapy and regenerative medicine approaches for conditions including tissue ischemia [7].…”