title: 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.
  
  
  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.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.forename: Masato
authors.initials: M
authors.lastname: Kanda
authors.forename: Mei-Lan
authors.initials: ML
authors.lastname: Liu
authors.forename: Naomichi
authors.initials: N
authors.lastname: Kondo
authors.forename: Atsuhiko T
authors.initials: AT
authors.lastname: Naito
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ogura
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
authors.forename: Jong-Kook
authors.initials: JK
authors.lastname: Lee
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D064591:Allografts; D000818:Animals; D006329:Heart Conduction System / Q000378:metabolism*; D008297:Male; D051379:Mice; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*