Pengaruh Pemberian Sekretom Sel Punca Mesenkimal Hipoksia pada Tikus Galur Wistar Model Stroke Iskemik Kajian pada Evaluasi Defisit Neurologis, Vascular Endothelial Growth Factor, Glial Fibrillary Acidic Protein, CD31 dan S100b

Abstract

Introduction: Currently, the standard treatments for ischemic stroke are intravenous thrombolysis and endovascular recanalization. In the acute phase (<4.5 hours), only 3.2 % to 5.2% of ischemic stroke patients are eligible for intravenous thrombolysis treatment. Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into different types of cells. MSCs will secrete secretomes that contain growth factors, chemokines, cytokines and bioactive lipids which is a potential therapy to improve neurological deficit in ischemic stroke. MSCs secretome promote the increasing production of CD31 and Vascular Endothelial Growth Factor (VEGF). Secretome hypoxia mesenchymal stem cells induce neurogenesis and angiogenesis effect from increasing the VEGF nad CD31 expression and reducing GFAP and S100B expression. Mechanisms above lead to cell regenerations and neurological function improvement in ischemic stroke. The aim of this study was to analyze the effect of 150 μl SHMSCs injection toward the increasing of VEGF and CD31 expression and decreasing of GFAP and S100B expression in Rattus norvegicus rats with ischemic stroke. Methods: A post-test-only experimental design with consecutive sampling was used, with 32 Rattus norvegicus as subjects. Secretome mesenchymal stem cells (SMSCs) under hypoxia condition were isolated from the umbilical cords of rats at 21 days of gestation. Assessment was carried out by measured the volume area infarction in rats’ brain and neurological improvement from mNSS in the sham group, control group (ischemic rats model with middle cerebral artery occlusion (MCAO) from CCA clamping), and resultant secretome was administered to ischemic rats subjected at doses of 150 μL (P1 group) and 300 μL (P2 group). Results: There are significantly diferrent between P2 group toward the increasing of VEGF (p = 0,028); CD31 (p = 0,031) also the decreasing of GFAP (p = 0,001); S100B (p = 0,029) and control group. There are also significantly diferrent in neuronal survival percentation from the measurement of volume area infarction between sham group ( p = 0,001), P1 ( p = 0,001), P2 ( p = 0,001) and control group also mNSS score between P2 (p = 0,003) and control group. Conclusion: SH-MSCs can induce cell proliferation, neuron cell survival, angiogenesis, vascularization, neurogenesis and blood-brain-barrier integrity recovery in rats’ brain through the increases of VEGF and CD31 expressions also the decreases of GFAP and S100B, which affects the reduction of infarction volume area and mNSS. These lead to neurological function and clinical improvement in ischemic stroke in rats.