Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells.

Abstract

BACKGROUND:

Adipose tissue is one of the sources of mesenchymal stem cells, which have the potential to differentiate into various types of cells, including myocytes. Whether brown adipose tissue (BAT)-derived cells might differentiate into the cardiac pacemaking-conducting cells, and have the potential to regenerate the cardiac conduction system (CCS), is investigated in this study.

METHODS AND RESULTS:

BAT was isolated from the interscapular area of mice and enzymatically digested before culture. Round or fusiform cells showed spontaneous beating at 4-7 days after culturing of BAT-derived cells. Reverse transcriptase-polymerase chain reaction analysis and immunocytochemical analysis revealed that BAT-derived cells expressed several cardiomyocytes, the CCS and pacemaker (PM) cell marker genes and proteins. Patch-clamp techniques revealed that spontaneous electrical activity and the shape of the action potential showed properties of cardiac PM cells. Next, a complete atrioventricular (AV) block was created in mice and green fluorescent protein-positive (GFP (+)) BAT-derived cells were injected intramyocardially around the AV node. At 1 week after transplantation, 50% of BAT-derived cells injected mice showed a sinus rhythm or a 2:1 AV block. Immunohistochemical analysis revealed that injected GFP (+) cells were engrafted and some GFP (+) cells co-expressed several cardiac PM cell marker proteins.

CONCLUSIONS:

BAT-derived cells differentiate into the CCS and PM-like cells in vitro and in vivo, and may become a useful cell source for arrhythmia therapy.

• Authors: Toshinao Takahashi, Toshio Nagai, Masato Kanda, Mei-Lan Liu, Naomichi Kondo, Atsuhiko T Naito, Takehiko Ogura, Haruaki Nakaya, Jong-Kook Lee, Issei Komuro, Yoshio Kobayashi
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 79 Issue 12 Pg. 2703-12 ( 2015) ISSN: 1347-4820 [Electronic] Japan
• PMID: 26411528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adipose Tissue, Brown (metabolism)
• Allografts
• Animals
• Heart Conduction System (metabolism)
• Male
• Mice
• Stem Cell Transplantation
• Stem Cells (metabolism)