title: Left atrial appendages from adult hearts contain a reservoir of diverse cardiac progenitor cells.
abstract: OBJECTIVE
  There is strong evidence supporting the claim that endogenous cardiac progenitor cells (CPCs) are key players in cardiac regeneration, but the anatomic source and phenotype of the master cardiac progenitors remains uncertain. Our aim was to investigate the different cardiac stem cell populations in the left atrial appendage (LAA) and their fates.
  
  
  RESULTS
  We investigated the CPC content and profile of adult murine LAAs using immunohistochemistry and flow cytometry. We demonstrate that the LAA contains a large number of CPCs relative to other areas of the heart, representing over 20% of the total cell number. We grew two distinct CPC populations from the LAA by varying the degree of proteolysis. These differed by their histological location, surface marker profiles and growth dynamics. Specifically, CD45(pos) cells grew with milder proteolysis, while CD45(neg) cells grew mainly with more intense proteolysis. Both cell types could be induced to differentiate into cells with cardiomyocyte markers and organelles, albeit by different protocols. Many CD45(pos) cells expressed CD45 initially and rapidly lost its expression while differentiating.
  
  
  CONCLUSIONS
  Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts. Two different types of CPCs were isolated, differing in their epicardial-myocardial localization. Considering studies demonstrating layer-specific origins of different cardiac progenitor cells, our findings may shed light on possible pathways to study and utilize the diversity of endogenous progenitor cells in the adult heart.
authors.affiliation: Cardiovascular Research Center, Heart Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Jussi V
authors.initials: JV
authors.lastname: Leinonen
authors.forename: Avishag K
authors.initials: AK
authors.lastname: Emanuelov
authors.forename: Yardanna
authors.initials: Y
authors.lastname: Platt
authors.forename: Yaron
authors.initials: Y
authors.lastname: Helman
authors.forename: Yael
authors.initials: Y
authors.lastname: Feinberg
authors.forename: Chaim
authors.initials: C
authors.lastname: Lotan
authors.forename: Ronen
authors.initials: R
authors.lastname: Beeri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D006325:Heart Atria / Q000166:cytology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D059748:Proteolysis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens
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