Bone-Marrow Mesenchymal Stem/Stromal Cells Have Enhanced Vasculogenic Potency Over Adipose Stem/Stromal Cells in Perfused In Vitro Cultures

Jun 29, 2022, 3:50 PM
Room: S2

Room: S2


Miettinen, Susanna (Adult Stem Cell Group, Faculty of Medicine and Health Technology, Tampere University )


Insufficient vascularization is a major obstacle for clinical application of tissue engineered transplants including bone. The ambition is to provide an environment rich in vascular networks to achieve efficient osseointegration and accelerate functional restoration after implantation. Of particular interest is the microvasculature that is crucial for oxygen and nutrient delivery. Microvascular networks in 3D can be formed in vitro through the co-culture of endothelial cells (ECs) with supporting pericytic cells. Mesenchymal stem/stromal cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ASCs) are an attractive choice for pericytes due to their natural perivascular localization and ability to support formation of mature and stable microvessels. Furthermore, they are most used cell types for bone tissue engineering and clinical trials focusing on bone regeneration.
Here, our aim was to explore the vasculogenic potential of human ASCs and BMSCs in a perfusable microfluidic device.
BMSCs and ASCs were co-cultured with ECs in a fibrin hydrogel in a microfluidic chip. We compared the capacity of BMSCs and ASCs to induce the formation of mature microvascular networks by ECs and to differentiate into pericytes. We studied the effect of MSCs on vessel characteristics such as area, diameter, length, and perfusability. Interstitial flow across the hydrogel area was measured daily in EC-BMSC and EC-ASC cocultures using fluorescence imaging. We assessed MSCs pericytic differentiation in terms of pericyte area and pericyte coverage by immunohistochemical staining and quantitative analysis. Furthermore, we evaluated the expression of main vasculogenesis related genes.
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. However, BMSCs induced formation of fully perfusable microvasculature with larger vessel area and vessel length compared to ASCs. Co-culture with ASCs resulted in only partially perfusable microvascular networks. Immunostainings revealed that BMSCs had greater potential to differentiate towards pericytes than ASCs. The gene expression analysis revealed significant differences in the expression of endothelial-specific and pericyte-specific genes, as well as genes involved in vasculature maturation and remodeling.
Overall, our study provides valuable knowledge on the properties of BMSCs and ASCs as vasculature supporting cells and highlights their distinct directing role in the regulation of microvascular phenotype that might have implications in bone tissue engineering applications.


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