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Published on: April 16, 2013
Patient characteristics and cell source determine the number of isolated human cardiac progenitor cells
Ayelet Itzhaki-Alfia1, Jonathan Leor, Ehud Raanani
1Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel.
Insights
The right atrium is the optimal source for isolating human cardiac progenitor cells (hCPCs), yielding more c-kit(+) and Islet-1(+) cells. Women also produced higher percentages of c-kit(+) cells from this source.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- Human cardiac progenitor cells (hCPCs) are crucial for myocardial regeneration.
- Optimal sources and patient factors influencing hCPC yield are not well-defined.
- Novel methods are needed to isolate and characterize hCPCs.
Purpose of the Study:
- To identify the best source of hCPCs for myocardial repair.
- To investigate the relationship between patient characteristics and hCPC number.
- To develop a novel method for hCPC isolation.
Main Methods:
- Developed a novel method to isolate hCPCs from surgical or biopsy samples.
- Cultured cells using stem cell expansion medium.
- Analyzed cell populations using fluorescence-activated cell sorting (FACS) and multivariable analysis.
Main Results:
- The right atrium yielded significantly higher percentages of c-kit(+) and Islet-1(+) cells compared to other cardiac chambers.
- Female sex and the right atrium as a source were associated with increased c-kit(+) cell numbers.
- Isolated hCPCs demonstrated multipotency and formed myocardial grafts after transplantation in rats.
Conclusions:
- The right atrium is the superior source for c-kit(+) and Islet-1(+) progenitor cells.
- Female patients yield a higher proportion of c-kit(+) cells.
- These findings advance strategies for cardiac regeneration using hCPCs.
Background:
The identification and isolation of human cardiac progenitor cells (hCPCs) offer new approaches for myocardial regeneration and repair. Still, the optimal source of human cardiac progenitor cells and the influence of patient characteristics on their number remain unclear. Using a novel method to isolate human cardiac progenitor cells, we aimed to define the optimal source and association between their number and patient characteristics.
Methods And Results:
We developed a novel isolation method that produced viable cells (7 x 10(6)+/-6.53 x 10(5)/g) from various tissue samples obtained during heart surgery or endomyocardial biopsies (113 samples from 94 patients 23 to 80 years of age). The isolated cardiac cells were grown in culture with a stem cell expansion medium. According to fluorescence-activated cell sorting analysis, cultured cells derived from the right atrium generated higher amounts of c-kit(+) (24+/-2.5%) and Islet-1(+) cells (7%) in culture (mean of passages 1, 2, and 3) than did cultured cells from the left atrium (7.3+/-3.5%), right ventricle (4.1+/-1.6%), and left ventricle (9.7+/-3%; P=0.001). According to multivariable analysis, the right atrium as the cell source and female sex were associated with a higher number of c-kit(+) cells. There was no overlap between c-kit(+) and Islet-1 expression. In vitro assays of differentiation into osteoblasts, adipocytes, and myogenic lineage showed that the isolated human cardiac progenitor cells were multipotent. Finally, the cells were transplanted into infarcted myocardium of rats and generated myocardial grafts.
Conclusions:
Our results show that the right atrium is the best source for c-kit(+) and Islet-1 progenitors, with higher percentages of c-kit(+) cells being produced by women.
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