Vasculogenic Potency of Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells Results in Differing Vascular Network Phenotypes in a Microfluidic Chip

Abstract

The vasculature is an essential, physiological element in virtually all human tissues. Formation of perfusable vasculature is therefore crucial for reliable tissue modeling. Three-dimensional vascular networks can be formed through the co-culture of endothelial cells (ECs) with stromal cells embedded in hydrogel. Mesenchymal stem/stromal cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ASCs) are an attractive choice as stromal cells due to their natural perivascular localization and ability to support formation of mature and stable microvessels in vitro. So far, BMSCs and ASCs have been compared as vasculature-supporting cells in static cultures. In this study, BMSCs and ASCs were co-cultured with endothelial cells in a fibrin hydrogel in a perfusable microfluidic chip. We demonstrated that using MSCs of different origin resulted in vascular networks with distinct phenotypes. Both types of MSCs supported formation of mature and interconnected microvascular networks-on-a-chip. However, BMSCs induced formation of fully perfusable microvasculature with larger vessel area and length whereas ASCs resulted in partially perfusable microvascular networks. Immunostainings revealed that BMSCs outperformed ASCs in pericytic characteristics. Moreover, co-culture with BMSCs resulted in significantly higher expression levels of endothelial and pericyte-specific genes, as well as genes involved in vasculature maturation. Overall, our study provides valuable knowledge on the properties of MSCs as vasculature-supporting cells and highlights the importance of choosing the application-specific stromal cell source for vascularized organotypic models.

Ascorbic Acid 2-Phosphate-Releasing Supercritical Carbon Dioxide-Foamed Poly(L-Lactide-Co-epsilon-Caprolactone) Scaffolds Support Urothelial Cell Growth and Enhance Human Adipose-Derived Stromal Cell Proliferation and Collagen Production

“…However, in addition to indicating smooth muscle cell diferentiation and presence of smooth muscle cells, αSMA is expressed by myofbroblasts [111]. It may also indicate pericytic and proangiogenic functions of hASC [112].…”

New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

“…Also, fibrin gel is used to support MVN formation in this study, consistent with its use in other self-organized perfusable MVNs formed in microfluidic devices. [78][79][80][81][82] Some studies, however, have used mixed matrices, such as fibrin/collagen and fibrin/matrigel mixture. Kim and colleagues were able to form perfusable MVNs in fibrin gel mixed with a low concentration of collagen I, [83] but others either failed [84] or found that pure fibrin gel scaffolds are preferable to collagen gel or collagen/fibrin combinations, because it significantly reduces matrix retractions during MVN maturation.…”

Immunotherapeutic Targeting of NG2/CSPG4 in Solid Organ Cancers

“…In the physiological adult pattern, NG2/CSPG4 is present in multiple adult organ tissues [ 22 ]. For example, in regard to vascular mural progenitor cells, NG2/CSPG4 is expressed on heart cardiomyocytes in large vessels, specifically smooth muscle cells (SMAs) [ 44 ], and on PCs in the microvasculature [ 45 ], making it even more meaningful for heart disease [ 46 ] than it has been in studies on the CNS. Based on the vital lessons learned from studies showing that NG2/CSPG4 is expressed in the vasculature of other adult organs, such as the liver [ 23 , 47 ], pancreas [ 48 ], lungs [ 49 ], kidneys [ 7 ], eyes [ 50 ], skin [ 51 ], and bone marrow [ 52 ], it is possible that the blood vessel walls harbor a reserve of NG2/CSPG4-expressing PCs as progenitor cells that may be integral to the elusive origin of mesenchymal stem cells (MSCs) [ 36 , 52 , 53 ] and other related adult solid tissue stem cells (SSCs).…”