Stem Cell Regeneration of the Vascular System in Progeria Mice

Heart, Lung, And Blood Institute

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Abstract

There are several populations of primitive cells in the circulation known as endothelial progenitor cells (EPCs) smooth muscle progenitor cells (SMPCs), hematopoietic stem cells (HSCs) and possibly other primitive cell populations. These stem/progenitor cells are all believed to originate in bone marrow and can collectively be referred to as bone marrow stem cells (BMSCs). BMSCs participate in the development of new blood vessels throughout adult life by a process referred to as neovascularization. As part of our continuing interest in cardiovascular disease, we propose to study the formation of new blood vessels in a mouse model of Hutchinson-Gilford Progeria Syndrome (HGPS). HGPS is a rare genetic disorder that affects 1:4,000,000 children and results in premature aging and death during the teenage years primarily as a result of cardiovascular disease. Transgenic progeria mice were created by insertion of a bacterial artificial chromosome that harbors the human mutant lamin A gene (LMNA) into the male pronucleus of C57BL/6 embryos. These HGPS mice are ideal for laboratory studies of cardiovascular disorders because of their inability to maintain viable smooth muscle cells in the tunica media layer of the great vessels including the aorta and carotid arteries. We plan to assess the level of incorporation of transplanted BMSCs from transgenic Enhanced Green Fluorescent Protein (EGFP) expressing mice into the expanding blood vessels of young adult HGPS mice. This study will involve a number of biochemical and histological analyses. We anticipate that information from this study will enable us to better understand the mechanism(s) by which new blood vessel growth is regulated. This may provide a foundation from which we can develop a model to analyze the potential role of bone marrow stem/progenitor cells in the treatment of cardiovascular diseases with an emphasis on children and young adults.