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Isolation of Perivascular Multipotent Precursor Cell Populations from Human Cardiac Tissue
Published on: October 8, 2016
Identification of a coronary stem cell in the human heart
Annarosa Leri1, Toru Hosoda, Jan Kajstura
1Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. aleri@partners.org
Insights
Vascular stem cells (VSCs) show promise for treating ischemic cardiomyopathy by regenerating damaged coronary arteries. This cell therapy approach could improve blood flow and prevent further heart damage.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Research
Background:
- Ischemic cardiomyopathy involves impaired coronary vasculature and myocardial perfusion despite myocyte regeneration.
- Existing treatments focus on partial recovery of damage, not prevention of injury.
Purpose of the Study:
- To investigate the therapeutic potential of vascular stem cells (VSCs) for ischemic cardiomyopathy.
- To evaluate VSCs' ability to restore coronary vasculature and improve myocardial perfusion.
Main Methods:
- Identification and characterization of VSCs expressing c-kit and KDR.
- Assessment of VSC self-renewal, clonogenicity, and multipotency in vitro and in vivo.
- Evaluation of VSC-induced vasculogenesis in animal models of coronary artery stenosis.
Main Results:
- VSCs demonstrated self-renewing, clonogenic, and multipotent properties.
- In animal models, VSCs formed new coronary arteries, partially restoring function of occluded vessels.
- Improved myocardial perfusion and mitigation of post-infarction myopathy were observed.
Conclusions:
- Vascular stem cells hold significant potential for cell therapy in ischemic heart disease.
- Restoring coronary circulation integrity with VSCs could shift therapeutic goals towards preventing myocardial injury.
Abstract:
Human ischemic cardiomyopathy is characterized by de novo cardiomyogenesis, which is limited to the surviving portion of the ventricle, and by organ hypertrophy that develops as a chronic response to ischemic injury. Although myocyte hypertrophy and myocyte regeneration restore the original myocardial mass, the coronary vasculature remains defective and the extent and regulation of myocardial perfusion are severely impaired. Recently, vascular stem cells (VSCs) have been identified in the coronary circulation. VSCs express c-kit and the vascular endothelial growth factor receptor-2, KDR. These cells are self-renewing, clonogenic, and multipotent in vitro and in vivo. In animal models of critical coronary artery stenosis, VSCs form large conductive coronary arteries and their distal branches. This degree of vasculogenesis replaces partly the function of the occluded coronary artery improving myocardial perfusion and positively interfering with the development of the post-infarction myopathy. Cell therapy directed to the restoration of the integrity of the coronary circulation, the replacement of atherosclerotic coronary vessels, or both, would change dramatically the goal of cell therapy for the ischemic heart: the prevention of myocardial injury would become the end-point of cell therapy rather than the partial recovery of established damage.

