期刊
BIOMATERIALS
卷 47, 期 -, 页码 1-12出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.12.043
关键词
Stem cell transplantation; Hyaluronic acid hydrogel; Growth factor sequestration; Neovascularization; Heparin; TGF beta 1
资金
- National Heart Lung and Blood Institute of the National Institutes of Health [R01HL096525]
- Siebel Stem Cell Institute Postdoctoral Fellowship
- UCSF Translational Cardiac Stem Cell Program
- Leone-Perkins Foundation
- Torian Foundation
- Vadasz Foundation
We have generated a bioinspired tunable system of hyaluronic acid (HyA)-based hydrogels for Matrix-Assisted Cell Transplantation (MACT). With this material, we have independently evaluated matrix parameters such as adhesion peptide density, mechanical properties, and growth factor sequestering capacity, to engineer an environment that imbues donor cells with a milieu that promotes survival and engraftment with host tissues after transplantation. Using a versatile population of Sca-1(+)/CD45(-) cardiac progenitor cells (CPCs), we demonstrated that the addition of heparin in the HyA hydrogels was necessary to coordinate the presentation of TGF beta 1 and to support the trophic functions of the CPCs via endothelial cell differentiation and vascular like tubular network formation. Presentation of exogenous TGF beta 1 by binding with heparin improved differentiated CPC function by sequestering additional endogenously-produced angiogenic factors. Finally, we demonstrated that TGF beta 1 and heparin-containing HyA hydrogels can promote CPC survival when implanted subcutaneously into murine hind-limbs and encouraged their participation in the ensuing neovascular response, which included blood vessels that had anastomosed with the host's blood vessels. (C) 2015 Elsevier Ltd. All rights reserved.
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