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Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
Patient profile modulates cardiac c-kit(+) progenitor cell availability and amplification potential
Elisa Gambini1, Maurizio Pesce, Luca Persico
1Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino-IRCCS, Milan, Italy. elisa.gambini@ccfm.it
Insights
Cardiovascular risk factors and medications impact cardiac progenitor cells (CPCs) isolation and growth. Patient profiles and treatments influence the therapeutic potential of these cells for cardiac repair.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Human cardiac progenitor cells (CPCs) expressing c-kit are crucial for cardiac repair.
- The influence of cardiovascular risk factors and medications on CPCs' ex vivo behavior is largely unknown.
Purpose of the Study:
- To investigate how cardiovascular risk factors and medications affect CPC isolation efficiency, c-kit expression, and proliferative potential.
- To identify clinical variables and treatments that modulate CPCs' ex vivo characteristics.
Main Methods:
- Cells from human right atrial appendages (n=50) were cultured and analyzed for CPC percentage and c-kit expression (MFI) using fluorescence activated cell sorting (FACS).
- CPCs were isolated and cultured for 4 passages (P4) to assess enrichment.
- Multiple linear regression analysis with stepwise selection identified associations between 19 clinical variables and CPCs' number, MFI, and enrichment.
Main Results:
- At T0, CPC number correlated with beta-blocker treatment, and c-kit expression correlated with pulmonary hypertension (PH).
- At P4, CPC enrichment inversely correlated with smoking, atrial fibrillation (AF), and myocardial infarction history.
- At P4, CPC enrichment positively correlated with PH and statin use.
Conclusions:
- Patient clinical profiles and medications significantly modulate the isolation and amplification of cardiac progenitor cells ex vivo.
- Understanding these modulations is essential for optimizing the therapeutic application of CPCs in cardiac repair.
- Findings suggest potential strategies to enhance or limitations to consider when using cardiac-resident progenitor cells therapeutically.
Abstract:
Human c-kit(+) cardiac progenitor cells (CPCs) are multipotent and may be used for cardiac repair. The effect of cardiovascular risk factors and medications on CPCs isolation efficiency, c-kit stem cell marker expression, and ex vivo proliferative potential is unknown and was examined in the present work. Cells from human right atrial appendages (n = 50) were expanded in culture; after ∼16 days (T0), it was established the percentage of CPCs and c-kit protein mean fluorescence intensity (MFI) by fluorescence activated cell sorting (FACS). Thereafter, CPCs were isolated by high throughput sorting; after culturing for 4 passages CPCs-derived cells were re-analyzed to assess c-kit(+) cell percentage and enrichment vs T0. The association between 19 demographic and clinical variables to CPCs number and MFI at T0, and CPCs enrichment at P4, was determined by multiple linear regression analysis with stepwise selection procedure. The results revealed that (1) at T0, the number of isolated CPCs directly correlated to β-blocker treatment; (2) at T0, c-kit protein expression directly correlated to pulmonary hypertension (PH); (3) at P4, CPC's enrichment inversely correlated to smoke, atrial fibrillation (AF), a history of myocardial infarction, whereas it directly correlated to PH and statins. Patient clinical profile and medications differently modulate CPCs isolation and amplification potential ex vivo. These results may provide new insights for the understanding of cardiac homeostasis and suggest both limitations and possible enhancing strategies for the therapeutic use of cardiac-resident progenitor cells.

