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Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
C-kit+ cardiac progenitors exhibit mesenchymal markers and preferential cardiovascular commitment
Elisa Gambini1, Giulio Pompilio, Andrea Biondi
1Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Via Parea 4, I-2018 Milan, Italy.
Insights
Cardiac c-kit(+) progenitors exhibit stem cell properties, differentiating into various cell types. These findings suggest a link between cardiac progenitors and heart-specific mesenchymal stem cells (MSCs).
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- The heart harbors c-kit(+) progenitor cells crucial for maintaining cardiac homeostasis.
- Cardiac c-kit(+) cells are multipotent, generating myocardial, endothelial, and smooth muscle cells.
- Recent studies suggest cardiac progenitor cells express mesenchymal stem cell (MSC) markers and possess MSC differentiation potential.
Purpose of the Study:
- To investigate if c-kit(+) cardiac progenitor cells share phenotypic and functional characteristics with cardiac MSCs.
- To explore the differentiation capacity of c-kit(+) cells in vitro and in vivo.
Main Methods:
- Enzymatic dissociation of heart auricle fragments to culture cells.
- Identification and sorting of c-kit(+) cells co-expressing MSC markers using flow cytometry.
- Immunofluorescence analysis of auricle tissue to detect c-kit(+) and MSC markers in vivo.
- Ex vivo expansion and differentiation induction of sorted c-kit(+) cells.
Main Results:
- A fibroblast-like cell population expressing mesenchymal markers was generated from heart auricles.
- C-kit(+) cells co-expressing MSC markers were identified both in vitro and in vivo.
- Ex vivo expanded c-kit(+) cells differentiated into osteoblasts, adipocytes, vascular smooth muscle cells, endothelium-like cells, and cardiac-like cells.
Conclusions:
- Cardiac c-kit(+) progenitors are primitive stem cells with multilineage differentiation capabilities.
- These findings support a potential relationship between cardiac c-kit(+) progenitors and a heart-specific MSC population.
- Cardiac c-kit(+) cells may possess cardiovascular commitment potential.
Aims:
The heart contains c-kit(+) progenitors that maintain cardiac homeostasis. Cardiac c-kit(+) cells are multipotent and give rise to myocardial, endothelial and smooth muscle cells, both in vitro and in vivo. C-kit(+) cells have been thoroughly investigated for their stem cell activity, susceptibility to stress conditions and ageing, as well as for their ability to repair the infarcted heart. Recently, expression of mesenchymal stem cell (MSC) markers and MSC differentiation potency have been reported in cardiac progenitor cells. Based on this evidence, we hypothesized that c-kit(+) cells may have phenotypic and functional features in common with cardiac MSCs.
Methods And Results:
Culture of cells obtained from enzymatic dissociation of heart auricle fragments produced a fast-growing fibroblast-like population expressing mesenchymal markers. C-kit(+) cells co-expressing MSC markers were identified in this population, sorted by flow cytometry and cultured in the presence or the absence of unselected cardiac cells from the same patients. Subsets of c-kit(+) cells also co-expressed MSCs markers in vivo, as detected by immunofluorescence analysis of auricle tissue. Ex vivo expanded c-kit(+) cells produced osteoblasts and adipocytes, although less preferentially than bone marrow-derived MSCs, possessed vascular smooth muscle cell features and were induced to differentiate into endothelium-like and cardiac-like cells.
Conclusion:
In line with previous findings, our results indicate that c-kit(+) cardiac progenitors are primitive stem cells endowed with multilineage differentiation ability. They further suggest a possible relationship between these cells and a heart-specific MSC population with cardiovascular commitment potential.

