4 research outputs found
Perivascular-like cells contribute to the stability of the vascular network of osteogenic tissue formed from cell sheet-based constructs
In recent years several studies have been supporting the existence of a close relationship in terms of function and progeny
between Mesenchymal Stem Cells (MSCs) and Pericytes. This concept has opened new perspectives for the application of
MSCs in Tissue Engineering (TE), with special interest for the pre-vascularization of cell dense constructs. In this work, cell
sheet technology was used to create a scaffold-free construct composed of osteogenic, endothelial and perivascular-like
(CD146+) cells for improved in vivo vessel formation, maturation and stability. The CD146 pericyte-associated phenotype
was induced from human bone marrow mesenchymal stem cells (hBMSCs) by the supplementation of standard culture
medium with TGF-b1. Co-cultured cell sheets were obtained by culturing perivascular-like (CD146+) cells and human
umbilical vein endothelial cells (HUVECs) on an hBMSCs monolayer maintained in osteogenic medium for 7 days. The
perivascular-like (CD146+) cells and the HUVECs migrated and organized over the collagen-rich osteogenic cell sheet,
suggesting the existence of cross-talk involving the co-cultured cell types. Furthermore the presence of that particular ECM
produced by the osteoblastic cells was shown to be the key regulator for the singular observed organization. The
osteogenic and angiogenic character of the proposed constructs was assessed in vivo. Immunohistochemistry analysis of
the explants revealed the integration of HUVECs with the host vasculature as well as the osteogenic potential of the created
construct, by the expression of osteocalcin. Additionally, the analysis of the diameter of human CD146 positive blood
vessels showed a higher mean vessel diameter for the co-cultured cell sheet condition, reinforcing the advantage of the
proposed model regarding blood vessels maturation and stability and for the in vitro pre-vascularization of TE constructs.Funding provided by Fundacao para a Ciencia e a Tecnologia project Skingineering (PTDC/SAU-OSM/099422/2008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript