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Updated: May 30, 2026
Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Rhesus monkey cardiosphere-derived cells for myocardial restoration
Andreas Martens1, Ina Gruh, Dimitrios Dimitroulis
1Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. martens.andreas@mh-hannover.de
Insights
Rhesus monkey cardiosphere-derived cells (RhCDC) proliferated in vivo and improved cardiac function after myocardial infarction. While RhCDC showed superior regenerative effects, a paracrine mechanism involving non-cellular factors was suggested.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Therapy
Background:
- Cardiosphere-derived cells (CDC) are a potential source for cardiac repair.
- The efficacy of CDC for myocardial restoration remains debated.
- Rhesus monkey CDC (RhCDC) have not been previously investigated in myocardial infarction models.
Purpose of the Study:
- To evaluate the survival, differentiation, and functional impact of RhCDC in a mouse model of myocardial infarction.
- To compare the effects of RhCDC with placebo and medium treatment.
- To elucidate the therapeutic mechanisms of RhCDC in cardiac repair.
Main Methods:
- RhCDC were isolated, characterized, and transplanted into SCID beige mice post-myocardial infarction.
- Left ventricular function was assessed using pressure-volume loop analysis.
- Cellular differentiation was analyzed via immunohistochemistry and RT-PCR.
Main Results:
- Transplanted RhCDC grafts proliferated in the infarcted myocardium.
- Both RhCDC and medium treatment improved left ventricular function and protected the infarct area.
- RhCDC demonstrated a superior regenerative effect compared to medium treatment alone.
Conclusions:
- RhCDC successfully engrafted and proliferated in vivo, influencing myocardial remodeling post-infarction.
- The observed benefits suggest a significant paracrine effect, potentially mediated by non-cellular components.
- RhCDC represent a promising cell source for sustained paracrine-based cardiac stem cell therapy.
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.
