Abstract
Recent studies suggest that whole bone marrow (WBM) derived stem cells may facilitate recovery following myocardial infarction. However, the sub-population of WBM responsible for recovery remains uncertain. By adjusting the abundance of CD34+LinNeg cells in human bone marrow we examined the relative significance of hematopoietic stem cells (HSC) in the recovery of cardiac function in a murine model of induced myocardial infarction. Enrichment of HSC by ~100-fold in WBM transplanted into mice significantly increased recovery of heart function and reduced scar size compared to transplantation of WBM depleted in HSC by ~10-fold (P P P P
Highlights
Myocardial infarction (MI) is the leading cause of disease mortality worldwide [1]
To determine whether the hematopoietic stem cells (HSC) population of bone marrow contributes to functional recovery after MI, we generated BM samples differing in their HSC content: HSC magnetic activated cell sorting (MACS) depleted, untreated whole bone marrow (WBM), and HSC MACS enriched
Human nuclear antigen (HNA) co-staining with DAPI was performed to evaluate whether cells with human nuclei had persisted to the experimental endpoint in the peri-infarct zone of hearts of mice receiving the transplanted BM samples
Summary
Myocardial infarction (MI) is the leading cause of disease mortality worldwide [1]. MI is a common consequence of cardiovascular disease (CVD) and results in either immediate death in the acute phase (AMI) or prolonged deterioration of cardiac function that leads to fatal cardiac failure or arrest in chronic cases. Adult stem cells may have shown the potential to reduce the near-term loss of life and regenerate heart function after MI in small scale clinical studies [2,3,4,5]. Bone marrow is the most studied accessible source of adult stem cells, and over the last decade bone marrow cells have been assessed for their capacity to regenerate heart tissue and function in both animals and humans. The mix of cell types within bone marrow has given rise to disagreements about the possible roles they could play in the regeneration of cardiac tissue. HSC reside primarily in bone marrow and give rise to all cells of the hematopoietic system. Extensive therapeutic utilization and the ability to purify HSC based on their defined surface phenotype makes them an attractive source of stem cells for cellular therapies
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