title: 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, which included blood vessels that had anastomosed with the host's blood vessels.
authors: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Material Science and Engineering, University of California, Berkeley, CA 94720, USA.
authors: Amit K
authors: AK
authors: Jha
authors: Department of Nutritional Science and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Kevin M
authors: KM
authors: Tharp
authors: Department of Medicine, University of California, San Francisco, CA 94143, USA.
authors: Jianqin
authors: J
authors: Ye
authors: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
authors: Jorge L
authors: JL
authors: Santiago-Ortiz
authors: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors: Wesley M
authors: WM
authors: Jackson
authors: Department of Nutritional Science and Toxicology, University of California, Berkeley, CA 94720, USA.
authors: Andreas
authors: A
authors: Stahl
authors: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
authors: David V
authors: DV
authors: Schaffer
authors: Department of Medicine, University of California, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
authors: Yerem
authors: Y
authors: Yeghiazarians
authors: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Material Science and Engineering, University of California, Berkeley, CA 94720, USA. Electronic address: kehealy@berkeley.edu.
authors: Kevin E
authors: KE
authors: Healy
mesh_terms: D000818:Animals; D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D006493:Heparin / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013314:Stress, Mechanical; D013438:Sulfhydryl Compounds / Q000737:chemistry; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D013438:Sulfhydryl Compounds; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D006493:Heparin
keywords: Growth factor sequestration; Heparin; Hyaluronic acid hydrogel; Neovascularization; Stem cell transplantation; TGFβ1