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Rhesus monkey cardiosphere-derived cells for myocardial restoration.
MedLine Citation:
PMID:  21843109     Owner:  NLM     Status:  In-Data-Review    
Abstract Background aims. 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.
Andreas Martens; Ina Gruh; Dimitrios Dimitroulis; Sebastian V Rojas; Ingrid Schmidt-Richter; Christian Rathert; Nawid Khaladj; Anke Gawol; Merab G Chikobava; Ulrich Martin; Axel Haverich; Ingo Kutschka
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cytotherapy     Volume:  13     ISSN:  1477-2566     ISO Abbreviation:  Cytotherapy     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100895309     Medline TA:  Cytotherapy     Country:  England    
Other Details:
Languages:  eng     Pagination:  864-72     Citation Subset:  IM    
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School , Hannover , Germany.
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