Human heart failure: is cell therapy a valid option?
Marcello Rota1, Annarosa Leri1, Piero Anversa1
1Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Insights
The adult heart can regenerate damaged cells, challenging the long-held belief that it is a non-renewable organ. Resident and bone marrow stem cells contribute to heart repair and renewal.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Research
Background:
- The heart was traditionally considered terminally differentiated and incapable of replacing damaged cardiomyocytes.
- Progressive myocyte loss with aging and scar formation post-myocardial infarction supported this view.
Purpose of the Study:
- To challenge the dogma of the heart as a non-renewable organ.
- To explore the regenerative capacity of the myocardium and the role of stem cells.
Main Methods:
- Review of emerging evidence on myocyte turnover and regeneration.
- Analysis of studies identifying dividing myocytes and resident stem cells.
- Investigation of exogenous progenitor cell differentiation.
Main Results:
- The adult heart exhibits cell death and restoration, crucial for homeostasis, aging, and disease.
- Dividing myocytes are present throughout life, regulated by resident stem cells.
- Exogenous progenitors, including those from bone marrow, can differentiate into cardiomyocyte and vascular lineages.
Conclusions:
- The heart is a self-renewing organ, not terminally differentiated.
- Resident and exogenous stem cells play a role in myocardial regeneration.
- This understanding underpins current cell-based therapies for cardiomyopathies.
Abstract:
The concept of the heart as a terminally differentiated organ incapable of replacing damaged myocytes has been at the center of cardiovascular research and therapeutic development for the past 50 years. The progressive decline in myocyte number with aging and the formation of scarred tissue following myocardial infarction have been interpreted as irrefutable proofs of the post-mitotic characteristics of the adult heart. However, emerging evidence supports a more dynamic view of the myocardium in which cell death and cell restoration are vital components of the remodeling process that governs organ homeostasis, aging and disease. The identification of dividing myocytes throughout the life span of the organisms and the recognition that undifferentiated primitive cells regulate myocyte turnover and tissue regeneration indicate that the heart is a self-renewing organ controlled by a compartment of resident stem cells. Moreover, exogenous progenitors of bone marrow origin transdifferentiate and acquire the cardiomyocyte and vascular lineages. This new reality constitutes the foundation of the numerous cell-based clinical trials that have been conducted in the last decade for the treatment of ischemic and non-ischemic cardiomyopathies.
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