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

Abstract

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, including blood vessels that had anastomosed with the host’s blood vessels.

Improving stem cell engraftment to enhance functional efficacy in cardiovascular disease: where are we now?

“…(Benoit et al, 2008;Kang et al, 2014). Subsequently, some scientists suggested that they will use hydrogel as a MACT to secrete growth factors and improve cell survival after transplantation (Jha et al, 2015). Hyaluronic acid -based hydrogel is a promising candidate which contains key advantages such as biocompatibility, tunable properties, and native biofunctionality (Highley et al, 2016;Travan et al, 2016).…”

“…Hyaluronic acid -based hydrogel is a promising candidate which contains key advantages such as biocompatibility, tunable properties, and native biofunctionality (Highley et al, 2016;Travan et al, 2016). It is wide used for biomedical applications, especially in heart disease treatment (Abdalla et al, 2013;Bonafe et al, 2014;Jha et al, 2015). More research is needed to validate its clinical potential as an adjunct to cellular engraftment therapies.…”

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

“…19,32,64,78 Biomaterial based deployment of EPCs has been shown to enhance efficacy of the transplanted cells by providing a microenvironment that enhances cell survival, function, and the sustained release and repopulation of the surrounding tissue by outwardly migrating cells. 70,78 Herein, researchers strive to develop biomaterial-based, synthetic ECMs as delivery vehicles for EPCs in order to enhance survival and retention for better tissue regeneration.…”

“…70,78 Herein, researchers strive to develop biomaterial-based, synthetic ECMs as delivery vehicles for EPCs in order to enhance survival and retention for better tissue regeneration. 32,39,79 Biomaterials can serve to create synthetic ECM--derived delivery vehicles that mediate biological processes, including cellular alignment and migration or growth factor release. 19,28 Tissue engineering strategies typically combine cells, polymeric scaffolds, chemical cues, and/or mechanical signals to guide cell phenotype.…”

“…58 While alginate is known to also have an affinity for heparinbinding proteins, other biomaterials are modified by incorporating heparin to tune protein binding and control release. 19,32 Herein, chemokine gradients were sustainably generated by incorporating SDF-1 within StarPEG-heparin hydrogels. 58 Here, the release profile of SDF-1 may be altered by precisely varying the loading concentration and by matrix metalloprotease (MMP)-mediated hydrogel cleavage.…”