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Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Bone marrow-derived B cells preserve ventricular function after acute myocardial infarction.
Traci T Goodchild1, Keith A Robinson, Wenxin Pang
1AC Therapeutics, Inc., Norcross, Georgia, USA.
JACC. Cardiovascular Interventions
|October 24, 2009
Summary
Mature B cells, a fraction of bone marrow mononuclear cells (MNCs), effectively promote cardiac repair post-myocardial infarction by preserving cardiomyocytes and improving heart function.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Immunology
Background:
- Bone marrow mononuclear cell (BM MNC) infusion shows potential for treating myocardial infarction (MI), but clinical results are inconsistent.
- BM MNCs comprise diverse cell types, including stem cells and mature leukocytes, each potentially contributing differently to repair.
- Understanding the role of specific mature cell subsets is crucial for optimizing cell-based cardiac repair therapies.
Purpose of the Study:
- To investigate the hypothesis that a specific subfraction of mature bone marrow mononuclear cells (MNCs) possesses potent cardiac repair capabilities post-infarction.
- To determine if mature cell subsets can enhance hematopoietic or resident stem cell-mediated cardiac repair.
- To evaluate the efficacy of isolated B cells and other mature cell subsets in promoting cardiac function and survival post-MI.
Main Methods:
- Isolation of stem cells (c-kit+) and mature cell subsets (myeloid, B, and T cells) from rat bone marrow.
- Induction of myocardial infarction in recipient rats followed by intramyocardial injection of cell subpopulations or saline.
- Assessment of cardiac function via echocardiography pre- and post-treatment, and analysis of cardiomyocyte apoptosis and proliferation.
Main Results:
- Injection of B cells, either fresh or cultured, significantly improved cardiac function (fractional ventricular diameter shortening) compared to saline.
- Cultured B cells demonstrated the most significant improvement in cardiac function (51% vs. 38% in saline controls).
- B cells markedly reduced cardiomyocyte apoptosis post-infarction, suggesting a protective mechanism.
Conclusions:
- Intramyocardial B cell administration preserves cardiac function post-ischemia through cardiomyocyte salvage.
- Mature B cells are a key effective component of bone marrow mononuclear cells for cardiac repair.
- Other bone marrow MNC subtypes were less effective or potentially detrimental to the cardioprotective effects of B cells.
