Evaluation of bone marrow derived stem cells in the treatment of acute myocardial infarction
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2011-08
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[Honolulu] : [University of Hawaii at Manoa], [August 2011]
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Abstract
Over the past decade the use of adult stem cells, particularly human bone marrow derived stem cells (BMSC), to safely facilitate recovery of cardiac function after myocardial infarctions has received a lot of interest and undergone experimentation in both animal models and clinical trials. The exact mechanism by which, and which cells of, the bone marrow contribute to this recovery remains unknown. This dissertation explores the ability and mechanism of human hematopoietic stem (HSC) cells within bone marrow to facilitate the recovery of cardiac function in a murine induced myocardial infarction model. We found that depleting the relative numbers of HSC in bone marrow by ~10-fold prior to transplantation into infarcted hearts resulted in a significant loss of left ventricular heart function compared to baseline assessment in vivo, as measured by echocardiography (p=0.03). This loss of heart function was indistinguishable from the loss experienced in control group that received no cells. In contrast, groups of mice that received either the whole bone marrow (WBM) sample of cells, or samples that were enriched for relative numbers of CD34+ cells by ~10-fold, showed no significant loss of heart function (p=0.19, p=0.08 respectively). The size of infarction was reduced in the group receiving HSC-enriched samples compared to the groups receiving either WBM (p=0.02), HSC depleted samples (p= 0.0001), and the control (p=0.02) group. Revascularization of the border zone of infarction by angiogenesis is a proposed mechanism for BMSC facilitation of recovery. We found increased capillary density in this border zone in the group receiving HSC enriched samples compared to the control (p= 0.0001) group and the group receiving HSC depleted samples (p= 0.001), a similar result was observed for group receiving WBM samples (p= 0.0003, p=0.006 respectively).
Together, these results show that treatment of induced myocardial infarction with human HSC can prevent the loss of heart function as assessed in vivo and ex vivo, and it is likely that angiogenesis-based reperfusion of the ischemic area partially responsible. The results imply that the use of autologous BM-derived samples enriched in HSC may markedly benefit treatment of heart disease.
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Ph.D. University of Hawaii at Manoa 2011.
Includes bibliographical references.
Includes bibliographical references.
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bone marrow
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Theses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Molecular Biosciences and Bioengineering.
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