Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies
Domenico D'Amario1, Claudia Fiorini, Patricia M Campbell
1Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. panversa@partners.org
Insights
Functionally competent cardiac stem cells (CSCs) of both myogenic (mCSC) and vasculogenic (vCSC) types can be isolated and expanded from small endomyocardial biopsies in patients with end-stage heart failure. These cells demonstrate robust growth properties, comparable to those from larger samples.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- Two distinct cardiac stem cell (CSC) populations, myogenic (mCSC) and vasculogenic (vCSC), are known in the human heart.
- The presence and functional capacity of these CSCs in end-stage cardiac failure patients, using small biopsy samples, remain unclear.
Purpose of the Study:
- To determine if a clinically significant number of mCSCs and vCSCs can be isolated and expanded from endomyocardial biopsies.
- To assess the feasibility of obtaining these cells from patients undergoing cardiac transplantation or left ventricular assist device implantation.
Main Methods:
- Endomyocardial biopsies were obtained from explanted hearts or during left ventricular assist device implantation.
- Cells were enzymatically dissociated, expanded, and sorted for c-kit (mCSCs) or c-kit/KDR (vCSCs).
- Characterization included growth rates, telomere length, telomerase activity, and differentiation potential.
Main Results:
- mCSCs and vCSCs comprised 97% and 3% of the c-kit population, respectively.
- Both cell types exhibited a population doubling time of approximately 27 hours, with 5x10^6 cells obtained in 28-41 days.
- CSCs showed significant growth potential, evidenced by high telomerase activity and long telomeres; mCSCs differentiated into cardiomyocytes, and vCSCs into endothelial/smooth muscle cells.
Conclusions:
- The isolation and expansion of functionally competent mCSCs and vCSCs from small endomyocardial biopsies are feasible in advanced heart failure patients.
- The growth characteristics of these CSCs are comparable to those derived from larger samples in non-failing hearts.
Rationale:
Two categories of cardiac stem cells (CSCs) with predominantly myogenic (mCSC) and vasculogenic (vCSC) properties have been characterized in the human heart. However, it is unknown whether functionally competent CSCs of both classes are present in the myocardium of patients affected by end-stage cardiac failure, and whether these cells can be harvested from relatively small myocardial samples.
Objective:
To establish whether a clinically relevant number of mCSCs and vCSCs can be isolated and expanded from endomyocardial biopsies of patients undergoing cardiac transplantation or left ventricular assist device implantation.
Methods And Results:
Endomyocardial biopsies were collected with a bioptome from the right side of the septum of explanted hearts or the apical LV core at the time of left ventricular assist device implantation. Two to 5 biopsies from each patient were enzymatically dissociated, and, after expansion, cells were sorted for c-kit (mCSCs) or c-kit and KDR (vCSCs) and characterized. mCSCs and vCSCs constituted 97% and 3% of the c-kit population, respectively. Population doubling time averaged 27 hours in mCSCs and vCSCs; 5×10(6) mCSCs and vCSCs were obtained in 28 and 41 days, respectively. Both CSC classes possessed significant growth reserve as documented by high telomerase activity and relatively long telomeres. mCSCs formed mostly cardiomyocytes, and vCSCs endothelial and smooth muscle cells.
Conclusions:
The growth properties of mCSCs and vCSCs isolated from endomyocardial biopsies from patients with advanced heart failure were comparable to those obtained previously from larger myocardial samples of patients undergoing elective cardiac surgery.
