Title

Transplanted embryonic stem cells following mouse myocardial infarction inhibit apoptosis and cardiac remodeling

Authors

Authors

D. K. Singla; G. E. Lyons;T. J. Kamp

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Am. J. Physiol.-Heart Circul. Physiol.

Keywords

cardiomyocytes; cell therapy; fibrosis; TIMP-1; HEART-FAILURE; OXIDATIVE STRESS; GENE-EXPRESSION; GROWTH-FACTORS; MYOCYTE DEATH; DIFFERENTIATION; REGENERATION; MATRIX; OVEREXPRESSION; ENHANCEMENT; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease

Abstract

We have previously shown that mouse embryonic stem ( ES) cells transplanted following myocardial infarction ( MI) differentiate into the major cell types in the heart and improve cardiac function. However, the extent of regeneration was relatively meager compared with the observed functional improvement. Therefore, we hypothesize that mechanisms in addition to regeneration contribute to the functional improvement from ES cell therapy. In this study, we examined the effect of mouse ES cells transplanted post-MI on cardiac apoptosis, fibrosis, and hypertrophy. MI was produced by left coronary artery ligation in C57BL/ 6 mice. Two different mouse ES cell lines, expressing enhanced green fluorescent protein and beta-galactosidase, respectively, were tested. Post-MI intramyocardial injection of 3 x 10(4) ES cells was compared with injection of medium alone. Terminal deoxynucleotidyl nick end labeling ( TUNEL), immunofluorescence, and histology were used to examine the effect of transplanted ES cells on apoptosis, fibrosis, and hypertrophy. Two weeks post-MI, ES cell-transplanted hearts exhibited a significant decrease in TUNEL-stained nuclei ( mean +/- SE; MI + medium = 12 +/- 1.5%; MI +/- ES cells = 6.6 +/- 1%, P < 0.05). TUNEL-positive nuclei were confirmed to be apoptotic by colabeling with a caspase-3 antibody. Cardiac fibrosis was 57% less in the MI + ES cell group compared with the MI + medium group ( P < 0.05) as shown with Masson's trichrome staining. Picrosirius red staining confirmed a decreased amount of collagen present in the MI + ES cell group. Cardiomyocyte hypertrophy was significantly decreased following ES cell transplantation compared with medium control animals. In conclusion, transplanted mouse ES cells in the infarcted heart inhibit apoptosis, fibrosis, and hypertrophy, thereby reducing adverse remodeling.

Journal Title

American Journal of Physiology-Heart and Circulatory Physiology

Volume

293

Issue/Number

2

Publication Date

1-1-2007

Document Type

Article

Language

English

First Page

H1308

Last Page

H1314

WOS Identifier

WOS:000248488000049

ISSN

0363-6135

Share

COinS