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The adult human heart relies on the function of about 5 billion beating heart cells. Cardiomyocytes, the specialized muscle cells power the heart’s contractions, are killed by heart attacks, blood clots, high blood pressure, and other factors of cardiovascular disease. Cardiomyocytes have an extremely limited capacity to be repaired or replaced naturally in the body, contributing to the severity and long-term effects of heart disease. Cardiovascular disease is sadly the leading cause of hospital admission and death in the United States, and ischemic heart disease is the leading cause of death and disability worldwide.
Severe damage is done to the organ tissue after a heart attack (also called myocardial infarction), leaving a scar in the muscle that does not contract, hindering the heart’s pumping function. Due to an insufficient means of tissue repair within an adult heart, the damage of a heart attack generally leads to a decline in heart function over time.
Cardiac stem cells are tissue-specific multipotent stem and progenitor cells capable of limited self-renewal and differentiation to coronary vessels and cardiomyocytes. Cardiac stem cells that reside in the adult heart govern myocardial homeostasis and repair injury through cardiogenesis (generation of cardiac cells) and angiogenesis (generation of blood vessels). Cardiac stem and progenitor cells hold great potential as a cell source for regenerative medicine applications around heart disease and heart failure, as these cells are proliferative yet committed to the cardiac fate, and importantly capable of further differentiation to all cells of the cardiac lineage.
However, cardiac stem cells and progenitor cells are found in very low numbers in the body. Additionally, cardiac stem and progenitor cells do not expand in culture long enough to generate a large enough quantity to be useful for regenerative cell therapy applications. In order to generate a sufficient amount of cardiac stem and progenitor cells for research, drug screening, and potential cell-based therapies, scientists must rely on creating the cells from other types of stem cells that can be expanded in much greater numbers.
Human pluripotent stem cells (hPSCs) are powerful stem cells that hold the potential to differentiate into any functional cell type in the body. hPSCs can directly differentiate fully specialized cardiomyocytes in the lab. However, due to the very limited ability of cardiomyocytes to divide and incorporate into a functional heart, these cells would not have a substantial impact on cardiac regeneration in vivo. Instead, research is focusing on differentiating hPSCs to cardiac stem cells and/or further specialized cardiac progenitor cells that are more capable of self-renewal and maturation after transplantation.
hPSCs are a critical tool for cardiovascular regeneration research due to their ability to directly differentiate into cardiac stem and progenitor cells, giving researchers the ability to transplant hPSC-derived cardiac stem cells to the site of injury, where they would mature and incorporate into existing heart tissue to support long-term cardiac function. There is significant promise in the use of functional cardiac stem and progenitor cells derived from human induced pluripotent stem cells (hiPSC) as healthy and disease-state biologic models for experimental studies and future cardiac cell therapy applications.
Human mesenchymal stem/stromal cells (MSCs) are also important and highly studied in the area of cardiac regeneration. MSCs can be isolated from multiple adult tissue types, including bone marrow, umbilical cord blood, and even adipose (fat) tissue, and multiple studies have demonstrated the ability of these cells to differentiate to cardiac stem- and progenitor-like cell types. More importantly than MSCs’ potential for cardiac lineage differentiation may be their innate ability to affect and promote the natural healing and cell maturation properties within the body through what is called the paracrine effect. MSCs are known to secrete natural chemical compounds, called cytokines, that provide essential cues for tissue repair in the body.
Transplanted MSCs secrete stimulatory cytokines that can initiate a natural regenerative response from the resident cardiac stem cells in the patient’s body. These cytokine signaling molecules promote the movement of healthy cells toward sites of inflammation and injury as part of the body’s immune response. MSCs have been shown to promote cardiac regeneration through multiple mechanisms, such as cardiomyocyte proliferation, cellular protection, vascularization, and limiting the inflammatory response and development of scar tissue after injury.
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June 2023 - Captivate Bio and EverCell Bio are excited to announce a new collaboration, delivering unique and custom stem cell services paired with custom reagents to accelerate research for discovery in regenerative medicine.
Neural stem cells (NSCs) are the stem cells of the nervous system. Learn how these cells are being applied in cell therapy applications and their importance in fighting neurodegenerative diseases.
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