title: Rhesus monkey cardiosphere-derived cells for myocardial restoration.
abstract: OBJECTIVE
  Cardiosphere-derived cells (CDC) have been proposed as a promising myocardial stem cell source for cardiac repair. They have been isolated from human, porcine and rodent cardiac biopsies. However, their usefulness for myocardial restoration remains controversial. We aimed to determine the survival, differentiation and functional effects of Rhesus monkey CDC (RhCDC) in a mouse model of myocardial infarction.
  
  
  METHODS
  RhCDC were isolated and characterized by flow cytometry and reverse transcriptase (RT)-polymerase chain reaction (PCR) and compared with human CDC. They were injected intramyocardially into severe combined immune deficiency (SCID) beige mice after ligature of the left anterior descending artery (LAD). Phosphate-buffered saline (PBS) served as placebo. Medium treatment alone was used to distinguish between cellular and non-cellular effects. Animals were divided into a non-infarcted control group (n = 7), infarct control groups (n = 24), medium-treated infarct groups (n = 35) and RhCDC-treated infarct groups (n = 33). Follow-up was either 1 or 4 weeks. LV function was assessed by pressure-volume loop analysis. Differentiation was analyzed by immunhistochemical profiling and RT-PCR.
  
  
  RESULTS
  Proliferating RhCDC grafts were detected after transplantation in an acute infarct model. RhCDC as well as medium treatment protected myocardium within the infarct area and improved LV function. RhCDC had a superior regenerative effect than medium alone.
  
  
  CONCLUSIONS
  For the first time, RhCDC have been used for the restoration of infarcted myocardium. RhCDC proliferated in vivo and positively influenced myocardial remodeling. This effect could be mimicked by treatment with unconditioned medium alone, emphasizing a non-cellular paracrine therapeutic mechanism. However, as a robust cardiac stem cell source, CDC might be useful to evoke prolonged paracrine actions in cardiac stem cell therapy.
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. martens.andreas@mh-hannover.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Martens
authors.forename: Ina
authors.initials: I
authors.lastname: Gruh
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Dimitroulis
authors.forename: Sebastian V
authors.initials: SV
authors.lastname: Rojas
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schmidt-Richter
authors.forename: Christian
authors.initials: C
authors.lastname: Rathert
authors.forename: Nawid
authors.initials: N
authors.lastname: Khaladj
authors.forename: Anke
authors.initials: A
authors.lastname: Gawol
authors.forename: Merab G
authors.initials: MG
authors.lastname: Chikobava
authors.forename: Ulrich
authors.initials: U
authors.lastname: Martin
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Ingo
authors.initials: I
authors.lastname: Kutschka
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology*; D033581:Stem Cell Transplantation / Q000379:methods*