MESENCHYMAL STEM CELL THERAPY'S IMPACT ON IL-11 EXPRESSION AND AUTOPHAGY REGULATION (AMPK, mTOR, ATG 5, ATG 12) IN A HIND LIMB ISCHEMIA MODEL

Introduction :ABSTRACTPeripheral Artery Disease (PAD), particularly Chronic Limb Threatening Ischemia (CLTI), is a serious condition resulting from the obstruction of blood flow to the lower extremities, which can lead to severe ischemia, ulcers, gangrene, and even amputation. Revascularization therapy has become the standard, but 20-30% of patients still experience poor clinical outcomes. Previous research focused on single angiogenesis without considering the autophagy and inflammation pathways. Umbilical Cord Mesenchymal Stem Cells (UCMSC) have emerged as a regenerative therapy with mechanisms that include autophagy, angiogenesis, immunomodulation, remodeling, and paracrine signaling. This study aims to analyze the effect of UCMSC on autophagy regulation, particularly involving the AMPK, mTOR, ATG5, and ATG12 pathways, as well as IL-11 expression and tissue function repair in a limb ischemia model.Method :The experimental study used 30 male Wistar rats divided into three groups: K1 (iliac-femoral artery ligation + UCMSC), K2 (iliac-femoral artery ligation + placebo), and K3 (control without ligation). UCMSC were administered intramuscularly in the gastrocnemius muscle in the ischemic area at a dose of 2×106 cells. The expression of AMPK, mTOR, ATG5, ATG12, IL-11, and VEGF proteins was measured using the Western Blot method on the gastrocnemius muscle tissue. Clinical evaluation includes motor function (Tarlov score) and degree of ischemia (modified ischemic score), conducted on the 1st and 2nd weeks post-ligation. Data were analyzed using the Mann Whitney and Wilcoxon tests with effect size calculations (Cohen’s d, Hedges’ g, Cliff’s delta).