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Emory University School of Medicine

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ACS Nano, September 11, 2014 | DOI: 10.1021/nn504617g Cell Therapy with Embryonic Stem Cell-Derived Cardiomyocytes Encapsulated in Injectable Nanomatrix Gel Enhances Cell Engraftment and Promotes Cardiac Repair

Abstract

Kiwon Ban^†⊥, Hun-Jun Park^†‡⊥, Sangsung Kim^†, Adinarayana Andukuri^†, Kyu-Won Cho^†, Jung Wook Hwang^†, Ho Jin Cha^†, Sang Yoon Kim^†, Woan-Sang Kim^†, Ho-Wook Jun^§, and Young-Sup Yoon^*†

^† Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, United States
^‡ Division of Cardiology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
^§ Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama 35203, United States

^⊥K. Ban and H.-J. Park have contributed equally to this report.

^*Correspondence to Young-Sup Yoon

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.

Keywords: PA-RGDS; myocardial infarction; pluripotent stem cell; cardiomyocyte; cardiac regeneration

논문정보

형식Research article
게재일2014년 09월 (BRIC 등록일 2014-09-22)
연구진국내+국외 연구진
분야 의약학 > 재생의학

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