Abstract 1708: The Induction of Experimental Type 1 Diabetes Led to the Loss of Ventricular Nestin(+) Neural-Like Stem Cells
Following myocardial infarction, resident ventricular nestin(+) neural-like stem cells migrate to the damaged region and may contribute to the intrinsic angiogenic and neurogenic response implicated in scar formation. It has been well established that impaired wound healing is a seminal pathological event of diabetes. The following study tested the hypothesis that the diabetic heart may be predisposed to maladaptive scar formation via the loss of ventricular nestin(+) neural-like stem cells. Type I diabetes was induced in male Sprague-Dawley rats by a single injection of streptozotocin (STZ; 60 mg/kg). Three weeks following STZ injection, diabetic rats (n=7) were associated with reduced body weight (STZ, 252±8; sham, 401±25 grams), elevated plasma glucose (STZ, 27±2 versus sham, 7±1 mM) and depressed left ventricular function (STZ versus sham; LVSP, 103±2 versus 146±9 mm Hg; +dP/dt, 5778±140 versus 6977±257 mm Hg/sec;-dP/dt, 3874±118 versus 6125±333 mm Hg/sec). Nestin protein (STZ, 0.13±0.02 versus sham, 0.54±0.09; n=4 for each group) and mRNA (STZ, 3.2±0.6 versus sham, 8.1±1; n=6 for each group) expression were significantly (p<0.01) reduced in the left ventricle of STZ-diabetic rats. An immunofluorescence approach revealed that the loss of nestin expression was attributed to the absence of ventricular nestin(+) neural-like stem cells in STZ-diabetic rats. In 3-week STZ-diabetic rats, long-acting insulin (3U/kg) was administered S.C. twice a day for a period of two weeks. Insulin administration to STZ-diabetic rats normalized plasma glucose 1 hour (10±2 mM) post-injection, remained decreased at 4 hours (17±2 mM) and returned to pre-injection hyperglycaemic levels 12 hours later. Furthermore, insulin therapy of STZ-diabetic rats partially restored the body weight loss (STZ, 252±8 versus STZ±insulin, 318±9 grams). Despite insulin treatment, depressed left ventricular function persisted, nestin mRNA (STZ, 3.2±0.6; STZ+insulin, 3.1±0.5) levels and the nestin(+) neural-like stem cell population remained significantly reduced in treated STZ-diabetic rats. The loss of ventricular nestin(+) neural-like stem cells suggests that scar formation following an ischemic insult may be compromised in the type I diabetic heart.