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Published on: September 3, 2020
The Roles of Bone Marrow-Derived Stem Cells in Coronary Collateral Growth Induced by Repetitive Ischemia
Molly Enrick1, Anurag Jamaiyar1, Vahagn Ohanyan1
1Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Insights
Bone marrow stem cells (BMSCs) promote coronary collateral growth in ischemic heart disease models. These cells are crucial for forming new blood vessels, improving heart function during ischemia.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Biology
Background:
- Ischemic heart diseases (IHD) have limited treatment options, with modest benefits from stem cell therapies.
- Coronary collateral growth (CCG) offers a natural bypass for IHD, but its regulation and the role of endogenous stem cells are unclear.
Purpose of the Study:
- To investigate the role of bone marrow stem cells (BMSCs) in regulating coronary collateral growth (CCG) in a rat model.
- To determine if BMSCs contribute to vascular repair and improved cardiac function following ischemic events.
Main Methods:
- Utilized a bone marrow transplantation model in GFP-transgenic rats to trace BMSCs.
- Induced repetitive ischemia (RI) in recipient rats and assessed cardiac function and blood flow via echocardiography.
- Analyzed BMSC homing, proliferation, differentiation, and engraftment in heart tissues using flow cytometry and imaging.
Main Results:
- BMSCs migrated to the collateral-dependent zone of the heart upon ischemic stimulation.
- Transplanted BMSCs differentiated into endothelial cells, contributing to collateral growth and improving coronary blood flow and cardiac function.
- Depletion of CD34+ BMSCs significantly impaired CCG, highlighting their essential role.
Conclusions:
- BMSCs play a critical role in promoting coronary collateral growth in response to ischemia.
- Targeting BMSC function represents a potential therapeutic strategy for treating ischemic heart diseases.
Abstract:
Many clinical trials have attempted to use stem cells to treat ischemic heart diseases (IHD), but the benefits have been modest. Though coronary collaterals can be a "natural bypass" for IHD patients, the regulation of coronary collateral growth (CCG) and the role of endogenous stem cells in CCG are not fully understood. In this study, we used a bone marrow transplantation scheme to study the role of bone marrow stem cells (BMSCs) in a rat model of CCG. Transgenic GFP rats were used to trace BMSCs after transplantation; GFP bone marrow was harvested or sorted for bone marrow transplantation. After recovering from transplantation, the recipient rats underwent 10 days of repetitive ischemia (RI), with echocardiography before and after RI, to measure cardiac function and myocardial blood flow. At the end of RI, the rats were sacrificed for the collection of bone marrow for flow cytometry or heart tissue for imaging analysis. Our study shows that upon RI stimulation, BMSCs homed to the recipient rat hearts' collateral-dependent zone (CZ), proliferated, differentiated into endothelial cells, and engrafted in the vascular wall for collateral growth. These RI-induced collaterals improved coronary blood flow and cardiac function in the recipients' hearts during ischemia. Depletion of donor CD34+ BMSCs led to impaired CCG in the recipient rats, indicating that this cell population is essential to the process. Overall, these results show that BMSCs contribute to CCG and suggest that regulation of the function of BMSCs to promote CCG might be a potential therapeutic approach for IHD.
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