Publication

Tgf-β1/cd105 signaling controls vascular network formation within growth factor sequestering hyaluronic acid hydrogels

Browne, Shane
Jha, Amit K.
Ameri, Kurosh
Marcus, Sivan G.
Yeghiazarians, Yerem
Healy, Kevin E.
Citation
Browne, Shane; Jha, Amit K. Ameri, Kurosh; Marcus, Sivan G.; Yeghiazarians, Yerem; Healy, Kevin E. (2018). Tgf-β1/cd105 signaling controls vascular network formation within growth factor sequestering hyaluronic acid hydrogels. PLOS ONE 13 (3),
Abstract
Cell-based strategies for the treatment of ischemic diseases are at the forefront of tissue engineering and regenerative medicine. Cell therapies purportedly can play a key role in the neovascularization of ischemic tissue; however, low survival and poor cell engraftment with the host vasculature following implantation limits their potential to treat ischemic diseases. To overcome these limitations, we previously developed a growth factor sequestering hyaluronic acid (HyA)-based hydrogel that enhanced transplanted mouse cardiosphere-derived cell survival and formation of vasculature that anastomosed with host vessels. In this work, we examined the mechanism by which HyA hydrogels presenting transforming growth factor beta-1 (TGF-beta 1) promoted proliferation of more clinically relevant human cardiospherederived cells (hCDC), and their formation of vascular-like networks in vitro. We observed hCDC proliferation and enhanced formation of vascular-like networks occurred in the presence of TGF-beta 1. Furthermore, production of nitric oxide (NO), VEGF, and a host of angiogenic factors were increased in the presence of TGF-beta 1. This response was dependent on the co-activity of CD105 (Endoglin) with the TGF-beta R2 receptor, demonstrating its role in the process of angiogenic differentiation and vascular organization of hCDC. These results demonstrated that hCDC form vascular-like networks in vitro, and that the induction of vascular networks by hCDC within growth factor sequestering HyA hydrogels was mediated by TGF-beta 1/CD105 signaling.
Funder
Publisher
Public Library of Science (PLoS)
Publisher DOI
10.1371/journal.pone.0194679
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland