Cell Therapy with Embryonic Stem Cell-Derived Cardiomyocytes Encapsulated in Injectable Nanomatrix Gel Enhances Cell Engraftment and Promotes Cardiac Repair

• Published in: ACS nano Vol. 8; no. 10; pp. 10815 - 10825
• Main Authors: Ban, Kiwon, Park, Hun-Jun, Kim, Sangsung, Andukuri, Adinarayana, Cho, Kyu-Won, Hwang, Jung Wook, Cha, Ho Jin, Kim, Sang Yoon, Kim, Woan-Sang, Jun, Ho-Wook, Yoon, Young-Sup
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 28.10.2014
• Subjects: Animals; Cell- and Tissue-Based Therapy; Embryonic Stem Cells - cytology; Encapsulation; Flow cytometry; Heart - physiopathology; Mice; Myocardial infarction; Myocytes, Cardiac - cytology; Nanostructure; Nanostructures; Peptides; Rats; Stem cells; Therapy; cardiac regeneration; PA-RGDS; pluripotent stem cell; myocardial infarction; cardiomyocyte
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/nn504617g

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.