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Enhanced survival and engraftment of transplanted stem cells using growth factor sequestering hydrogels

Jha, Amit K., Tharp, Kevin M., Ye, Jianqin, Santiago-Ortiz, Jorge L., Jackson, Wesley M., Stahl, Andreas, Schaffer, David V., Yeghiazarians, Yerem, Healy, Kevin E.
Biomaterials 2015 v.47 pp. 1-12
adhesion, blood vessels, cell differentiation, cell transplantation, endothelial cells, heparin, hindlimbs, hyaluronic acid, hydrogels, mechanical properties, mice, stem cells, tissues, transforming growth factor beta 1
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 TGFβ1 and to support the trophic functions of the CPCs via endothelial cell differentiation and vascular like tubular network formation. Presentation of exogenous TGFβ1 by binding with heparin improved differentiated CPC function by sequestering additional endogenously-produced angiogenic factors. Finally, we demonstrated that TGFβ1 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.