title: The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair.
abstract: OBJECTIVE
  Considerable shortcomings in the treatment of myocardial infarction (MI) still exist and therefore mortality remains high. Cardiac stem cell (CSC) therapy is a promising approach for myocardial repair. However, identification and isolation of candidate CSCs is mainly based on the presence or absence of certain cell surface markers, which suffers from some drawbacks. In order to find a more specific and reliable identification and isolation method, we investigated whether CSCs can be isolated based on the high expression of aldehyde dehydrogenase (ALDH).
  
  
  RESULTS
  An ALDH(+) stem cell population, the cardiac atrial appendage stem cells (CASCs), was isolated from human atrial appendages. CASCs possess a unique phenotype that is clearly different from c-kit(+) CSCs but that seems more related to the recently described cardiac colony-forming-unit fibroblasts. Based on immunophenotype and in vitro differentiation studies, we suggest that CASCs are an intrinsic stem cell population and are not mobilized from bone marrow or peripheral blood. Indeed, they possess a clonogenicity of 16% and express pluripotency-associated genes. Furthermore, compared with cardiosphere-derived cells, CASCs possess an enhanced cardiac differentiation capacity. Indeed, differentiated cells express the most important cardiac-specific genes, produce troponin T proteins, and have an electrophysiological behaviour similar to that of adult cardiomyocytes (CMs). Transplanting CASCs in the minipig MI model resulted in extensive cardiomyogenic differentiation without teratoma formation.
  
  
  CONCLUSIONS
  We have identified a new human CSC population able to differentiate into functional CMs. This opens interesting perspectives for cell therapy in patients with ischaemic heart disease.
authors.affiliation: Laboratory of Experimental Hematology,  Jessa Hospital, 3500 Hasselt,  Belgium.
authors.forename: Remco
authors.initials: R
authors.lastname: Koninckx
authors.forename: Annick
authors.initials: A
authors.lastname: Daniëls
authors.forename: Severina
authors.initials: S
authors.lastname: Windmolders
authors.forename: Urbain
authors.initials: U
authors.lastname: Mees
authors.forename: Regina
authors.initials: R
authors.lastname: Macianskiene
authors.forename: Kanigula
authors.initials: K
authors.lastname: Mubagwa
authors.forename: Paul
authors.initials: P
authors.lastname: Steels
authors.forename: Luc
authors.initials: L
authors.lastname: Jamaer
authors.forename: Jasperina
authors.initials: J
authors.lastname: Dubois
authors.forename: Boris
authors.initials: B
authors.lastname: Robic
authors.forename: Marc
authors.initials: M
authors.lastname: Hendrikx
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Rummens
authors.forename: Karen
authors.initials: K
authors.lastname: Hensen
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D020517:Atrial Appendage / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D009203:Myocardial Infarction / Q000628:therapy*; D017202:Myocardial Ischemia / Q000628:therapy*; D010641:Phenotype; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome
chemical_list: D000444:Aldehyde Dehydrogenase