title: Keratose Hydrogels Promote Vascular Smooth Muscle Differentiation from C-kit-Positive Human Cardiac Stem Cells.
abstract: Stem cell-based therapies have demonstrated great potential for the treatment of cardiac diseases, for example, myocardial infarction; however, low cell viability, low retention/engraftment, and uncontrollable in vivo differentiation after transplantation are still major limitations, which lead to low therapeutic efficiency. Biomaterials provide a promising solution to overcome these issues due to their biocompatibility, biodegradability, low/nonimmunogenicity, and low/noncytotoxicity. The present study aimed to investigate the impacts of keratose (KOS) hydrogel biomaterial on cellular viability, proliferation, and differentiation of c-kit+human cardiac stem cells (hCSCs). Briefly, hCSCs were cultured on both KOS hydrogel-coated dishes and regular tissue culture dishes (Blank control). Cell viability, stemness, proliferation, cellular morphology, and cardiac lineage differentiation were compared between KOS hydrogel and the Blank control at different time points. We found that KOS hydrogel is effective in maintaining hCSCs without any observable toxic effects, although cell size and proliferation rate appeared smaller on the KOS hydrogel compared to the Blank control. To our surprise, KOS hydrogel significantly promoted vascular smooth muscle cell (VSMC) differentiation (∼72%), while on the Blank control dishes, most of the hCSCs (∼78%) became cardiomyocytes. Furthermore, we also observed "endothelial cell tube-like" microstructures formed by differentiated VSMCs only on KOS hydrogel, suggesting a potential capability of the hCSC-derived VSMCs for in vitro angiogenesis. To the best of our knowledge, this is the first report to discover the preferred differentiation of hCSCs toward VSMCs on KOS hydrogel. The underlying mechanism remains unknown. This innovative methodology may offer a new approach to generate a robust number of VSMCs simply by culturing hCSCs on KOS hydrogel, and the resulting VSMCs may be used in animal studies and clinical trials in combination with an injectable KOS hydrogel to treat cardiovascular diseases.
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine , Virginia Tech, Blacksburg, Virginia.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Ledford
authors.affiliation: 2 Department of Biomedical Engineering and Mechanics, School of Biomedical Engineering and Sciences , Virginia Tech, Blacksburg, Virginia.
authors.forename: Jamelle
authors.initials: J
authors.lastname: Simmons
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine , Virginia Tech, Blacksburg, Virginia.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: 3 Research Institute of Heart Failure, Shanghai East Hospital of Tongji University , Shanghai, People's Republic of China .
authors.forename: Huimin
authors.initials: H
authors.lastname: Fan
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine , Virginia Tech, Blacksburg, Virginia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Barron
authors.affiliation: 3 Research Institute of Heart Failure, Shanghai East Hospital of Tongji University , Shanghai, People's Republic of China .
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 2 Department of Biomedical Engineering and Mechanics, School of Biomedical Engineering and Sciences , Virginia Tech, Blacksburg, Virginia.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Dyke
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine , Virginia Tech, Blacksburg, Virginia.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: He
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D020100:Hydrogels; D019009:Proto-Oncogene Proteins c-kit
keywords: c-kit+ human cardiac stem cells; cardiac lineage differentiation; hydrogel biomaterial; keratin or keratose; vascular smooth muscle cells