Transplantation of mesenchymal stem cells improves atrioventricular conduction in a rat model of complete atrioventricular block.
Mesenchymal stem cells (MSCs) are multipotent cells that differentiate into a variety of lineages including myocytes and vascular endothelial cells. However, little information is available regarding the therapeutic potential of MSCs in patients with atrioventricular block (AVB). We investigated whether local implantation of MSCs improves AV conduction in a rat model of complete AVB. Complete AVB was achieved by injection of ethanol into the AV nodal region of Lewis rats. Five days after ethanol injection, 2 x 10(6) of MSCs (MSC group) or vehicle (Control group) were injected into the AV nodal region. Animals were monitored by electrocardiograms for 14 days, and physiological and histological examinations were performed. The 1:1 AV conduction was recovered in 5 of 15 rats (33%) in the MSC group during the followup period, whereas no improvement was observed in the control group. MSC transplantation significantly decreased collagen deposition in the AV node, which was associated with a marked decrease in transforming growth factor-beta1 expression. In vitro experiments demonstrated that MSCs secreted a large amount of antifibrotic factors such as hepatocyte growth factor and interleukin-10, and MSC conditioned medium inhibited the growth of adult cardiac fibroblasts. In addition, local injection of MSC conditioned medium recovered AV conduction in 2 of 15 rats (13%). MSC transplantation improved AV conduction in a rat model of complete AVB, at least in part through antifibrotic paracrine effects.
Yokokawa
Milki
M
Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan.
Ohnishi
Shunsuke
S
Ishibashi-Ueda
Hatsue
H
Obata
Hiroaki
H
Otani
Kentaro
K
Miyahara
Yoshinori
Y
Tanaka
Koichi
K
Shimizu
Wataru
W
Nakazawa
Kazuo
K
Kangawa
Kenji
K
Kamakura
Shiro
S
Kitamura
Soichiro
S
Nagaya
Noritoshi
N
D000818:Animals; D054537:Atrioventricular Block / Q000503:physiopathology / Q000628:therapy*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000662:veterinary; D004719:Endomyocardial Fibrosis / Q000517:prevention & control; D005347:Fibroblasts / Q000502:physiology; D006329:Heart Conduction System / Q000503:physiopathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000662:veterinary; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology