Microvascular Networks From Endothelial Cells and Mesenchymal Stromal Cells From Adipose Tissue and Bone Marrow: A Comparison

Abstract

A promising approach to overcome hypoxic conditions in tissue engineered constructs is to use the potential of endothelial cells (EC) to form networks in vitro when co-cultured with a supporting cell type in a 3D environment. Adipose tissue-derived stromal cells (ASC) as well as bone marrow-derived stromal cells (BMSC) have been shown to support vessel formation of EC in vitro, but only very few studies compared the angiogenic potential of both cell types using the same model. Here, we aimed at investigating the ability of ASC and BMSC to induce network formation of EC in a co-culture model in fibrin. While vascular structures of BMSC and EC remained stable over the course of 3 weeks, ASC-EC co-cultures developed more junctions and higher network density within the same time frame. Both co-cultures showed positive staining for neural glial antigen 2 (NG2) and basal lamina proteins. This indicates that vessels matured and were surrounded by perivascular cells as well as matrix molecules involved in stabilization. Gene expression analysis revealed a significant increase of vascular endothelial growth factor (VEGF) expression in ASC-EC co-culture compared to BMSC-EC co-culture. These observations were donor-independent and highlight the importance of organotypic cell sources for vascular tissue engineering.

Deciphering the relative roles of matrix metalloproteinase‐ and plasmin‐mediated matrix degradation during capillary morphogenesis using engineered hydrogels

“…This model mimics vascularization strategies often deployed for tissue engineering applications that involve injection of populations of cells or pre‐patterned cell aggregates that organize into microvasculature. The phenotype and angiogenic potential of microvascular ECs and stromal cells vary widely according to their origin. We chose umbilical vein‐derived ECs and supporting cells derived from bone marrow, lung, and dermis to explore in our model because our prior work has suggested differential utilization of MMP‐ and plasmin‐mediated proteolysis with these combinations .…”

SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema

“…Deregulation of miR-188-5p might hence contribute to the endothelial barrier dysfunction and lymphangiopathy, which has been described in lipedema 44 . This suggests also a potential involvement of the mesenchymal stem cell populations of the SVF in the progression of lipedema, which are participating in the formation and stabilization of vessels 45 . It has been demonstrated that the total number of circulating particles (incl.…”

Ex vivo engineering of blood and lymphatic microvascular networks

“…Nevertheless, this difficulty can be mastered by binding of cell recognition motifs in form of small immobilized peptides such as the RGD sequence, which stimulates cell adhesion via integrins (11). The most employed natural scaffolds for engineering vascular networks are collagens (12,13) or fibrin matrices (14,15,16). These types of scaffolds have a high degree of biocompatibility and provide superior adhesion sites leading to improved growth and differentiation capability of the cells (17).…”

“…Initially, fibroblasts were utilized as supporting cell types for capillary formation in co-culture with ECs (16,25). Later, also mesenchymal stromal/stem cells (MSCs) mainly from bone marrow (14,26) and adipose tissue Overview of different vascularization strategies. Functional blood and lymphatic microvasculature can be achieved by co-culturing of endothelial and supporting cells from different origins.…”