Abstract 184: Alterations in Tissue-Based Sca-1+ Stem Cell Populations in Diabetic Arteries

Abstract

Objectives: The stem cell antigen-1 (Sca-1) progenitor cell is a pluripotent stem cell that is implicated in homeostasis of the vascular wall, including regulation of the response to injury. Diabetic mice have a decreased Sca-1+ bone marrow population, but it is not known how the diabetic state affects the permanent tissue-based Sca-1+ population. We hypothesize that diabetic mice have a decreased Sca-1+ stem cell population in the arterial wall compared to wild type mice. Methods: Arteries were harvested from male C57BL/6 wild type (WT) and Lepr Db/db diabetic (DB) mice (n=4-6/strain). Diabetic state was confirmed in DB mice by measuring serum insulin and glucose levels. Harvested segments included carotid, thoracic aorta, abdominal aorta, and femoral arteries. Arteries underwent immunofluorescent staining for Sca-1. Staining in the adventitia, media and intima was assessed by blinded grading (scale of 0-4). Results: Sca-1+ stem cells were predominantly located in the adventitial layer of the arterial wall in both WT and DB mice (7.2-fold vs. media, 3.5-fold vs. intima). In the carotid artery, DB mice demonstrated 26% less adventitial Sca-1+ staining than WT mice (1.69±0.1 vs. 2.27±0.1, P≤0.001). In the thoracic aorta, DB mice had 28% less adventitial Sca-1+ staining than WT mice (2.06±.0.1 vs. 2.88±0.1, P≤0.001). Notably, no significant difference was detected in adventitial Sca-1+ staining in the abdominal aorta or femoral arteries between the mouse strains. In the media, DB mice showed a trend towards increased Sca-1+ staining; this only reached significance in the abdominal aorta (0.55±0.1 vs. 0.22±0.1, P=0.011). In the intima, there was a trend towards increased Sca-1+ staining in DB mice among all arterial segments, but this did not reach statistical significance. Conclusions: Diabetic mice demonstrate a depleted Sca-1+ stem cell population in the adventitia of the carotid artery and thoracic aorta compared to WT counterparts. In contrast, diabetic mice showed an increased Sca-1+ population in the media of the abdominal aorta. This overall decrease in the adventitial Sca-1+ stem cells of diabetic mice and shift in distribution amongst the arterial wall layers may contribute to the altered homeostasis and response to injury in diabetic vessels.