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.
Highlights
One of the major limitations of tissue engineered constructs is their need of a vascular system once they are implanted in vivo, as the diffusion limit of oxygen is smaller than 200 μm (Jain et al, 2005)
The objective of this study was to investigate how mesenchymal stromal cells (MSC) populations derived from different tissues influence vascular network formation, maturation and gene expression of endothelial cells (EC)
We show that while maturation of vascular networks in terms of coverage with neural glial antigen 2 (NG2) expressing cells as well as basal lamina protein formation is similar in adipose tissue-derived stromal cells (ASC)+EC and bone marrow-derived stromal cells (BMSC)+EC co-cultures, there are significant differences in vascular network density and gene expression
Summary
One of the major limitations of tissue engineered constructs is their need of a vascular system once they are implanted in vivo, as the diffusion limit of oxygen is smaller than 200 μm (Jain et al, 2005). ASC- and BMSC-Derived Vascular Networks network upon implantation in vivo (Melero-Martin et al, 2008; Reinisch et al, 2009; Traktuev et al, 2009; Unger et al, 2010; Verseijden et al, 2010a, 2012; Pill et al, 2015; Tiruvannamalai Annamalai et al, 2016). The vascular structures matured over time by surrounding themselves with perivascular cells and forming a physiological basal lamina in vitro (Pill et al, 2015; Tiruvannamalai Annamalai et al, 2016)
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