title: Cell therapy with embryonic stem cell-derived cardiomyocytes encapsulated in injectable nanomatrix gel enhances cell engraftment and promotes cardiac repair.
abstract: A significant barrier to the therapeutic use of stem cells is poor cell retention in vivo. Here, we evaluate the therapeutic potential and long-term engraftment of cardiomyocytes (CMs) derived from mouse embryonic stem cells (mESCs) encapsulated in an injectable nanomatrix gel consisting of peptide amphiphiles incorporating cell adhesive ligand Arg-Gly-Asp-Ser (PA-RGDS) in experimental myocardial infarction (MI). We cultured rat neonatal CMs in PA-RGDS for 7 days and found that more than 90% of the CMs survived. Next, we intramyocardially injected mouse CM cell line HL-1 CMs with or without PA-RGDS into uninjured hearts. Histologic examination and flow cytometry analysis of digested heart tissues showed approximately 3-fold higher engraftment in the mice that received CMs with PA-RGDS compared to those without PA-RGDS. We further investigated the therapeutic effects and long-term engraftment of mESC-CMs with PA-RGDS on MI in comparison with PBS control, CM-only, and PA-RGDS only. Echocardiography demonstrated that the CM-only and CM+PA-RGDS groups showed higher cardiac function at week 2 compared to other groups. However, from 3 weeks, higher cardiac function was maintained only in the CM+PA-RGDS group; this was sustained for 12 weeks. Confocal microscopic examination of the cardiac tissues harvested at 14 weeks demonstrated sustained engraftment and integration of mESC-CMs into host myocardium in the CM+PA-RGDS group only. This study for the first time demonstrated that PA-RGDS encapsulation can enhance survival of mESC-derived CMs and improve cardiac function post-MI. This nanomatrix gel-mediated stem cell therapy can be a promising option for treating MI.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University School of Medicine , Atlanta, Georgia 30322, United States.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Ban
authors.forename: Hun-Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Sangsung
authors.initials: S
authors.lastname: Kim
authors.forename: Adinarayana
authors.initials: A
authors.lastname: Andukuri
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Hwang
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Cha
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Woan-Sang
authors.initials: WS
authors.lastname: Kim
authors.forename: Ho-Wook
authors.initials: HW
authors.lastname: Jun
authors.forename: Young-Sup
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D053595:Embryonic Stem Cells / Q000166:cytology*; D006321:Heart / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D049329:Nanostructures; D051381:Rats
keywords: PA-RGDS; cardiac regeneration; cardiomyocyte; myocardial infarction; pluripotent stem cell