title: Exploiting AT2R to Improve CD117 Stem Cell Function In Vitro and In Vivo--Perspectives for Cardiac Stem Cell Therapy.
abstract: OBJECTIVE
  CD117(+) stem cell (SC) based therapy is considered an alternative therapeutic option for terminal heart disease. However, controversies exist on the effects of CD117(+) SC implantation. In particular, the link between CD117(+) SC function and angiotensin-II-type-2 receptor (AT2R) after MI is continuously discussed. We therefore asked whether 1) AT2R stimulation influences CD117(+) SC properties in vitro and, 2) which effects can be ascribed to AT2R stimulation in vivo.
  
  
  METHODS
  We approached AT2R stimulation with Angiotensin II while simultaneously blocking its opponent receptor AT1 with Losartan. CD117 effects were dissected using a 2D-Matrigel assay and HL-1 co-culture in vitro. A model of myocardial infarction, in which we implanted EGFP(+) CD117 SC, was further applied.
  
  
  RESULTS
  While we found indications for AT2R driven vasculogenesis in vitro, co-culture experiments revealed that CD117(+) SC improve vitality of cardiomyocytes independently of AT2R function. Likewise, untreated CD117(+) SC had a positive effect on cardiac function and acted cardioprotective in vivo.
  
  
  CONCLUSIONS
  Therefore, our data show that transient AT2R stimulation does not significantly add to the beneficial actions of CD117(+) SC in vivo. Yet, exploiting AT2R driven vasculogenis via an optimized AT2R stimulation protocol may become a promising tool for cardiac SC therapy.
authors: Reference and Translation Centre for Cardiac Stem Cell Therapy (RTC)/Department of Cardiac Surgery, University of Rostock, Germany.
authors: Marion
authors: M
authors: Ludwig
authors: Anita
authors: A
authors: Tölk
authors: Anna
authors: A
authors: Skorska
authors: Christian
authors: C
authors: Maschmeier
authors: Ralf
authors: R
authors: Gaebel
authors: Cornelia Aquilina
authors: CA
authors: Lux
authors: Gustav
authors: G
authors: Steinhoff
authors: Robert
authors: R
authors: David
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D018920:Coculture Techniques / Q000379:methods; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*
chemical_list: D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019009:Proto-Oncogene Proteins c-kit; D019808:Losartan