Pengaruh Pemberian Sekretom Sel Punca Mesenchymal Hipoksia terhadap Ekspresi Gen Vascular Endothelial Derived Growth Factor (VEGF), Platelet Derived Growth Factor (PDGF), Thrombospondin-4 (TSP-4) dan Angiogenesis pada Tikus Model Diabetes Mellitus dengan Hindlimb Ischemia

Abstract

Introduction: Diabetes is a major health problem in the world where one of the complications is Peripheral Arterial Disease (PAD). Mesenchymal stem cells are reported to have several growth factors that play a role in the angiogenesis process. The purpose of this study was to prove the effect of Hypoxic Mesenchymal Stem Cell Secretome (HMSCS) on angiogenic growth factors Vascular Endothelial Derived Growth Factor (VEGF), Platelet Derived Growth Factor (PDGF), Thrombospondin-4 (TSP-4) and the degree of angiogenesis through CD-31, α- SMA, and collagen in a rat model of Diabetes Mellitus (DM) with Hind Limb Ischemia (HLI). Methods: HMSCS was isolated from the umbilical cord of rats and cultured in a hypoxic chamber with 5% O2 for 24 hours. The subjects in this study were rats of the Wistar strain which were induced by streptozotocin 60mg/KgBW intraperitoneally and left femoral artery ligation was performed. a total of 24 rats were divided into 4 groups, namely: the Sham group, the control group, the HMSCS group at a dose of 200μl (P1), and the SSPMH group at a dose of 400μl (P2). Expression of VEGF, PDGF, TSP-4 was examined by RT-PCR examination on day 14 after administration of HMSCS. While the expression of CD31. α-SMA, examined using immunohistochemistry and Masson's Thricrome staining. Results: TSP-4 gene expression was found to be significantly higher at a dose of 400 μl (p<0.05) and there was no significant difference in the expression of VEGF and PDGF. The expression of CD31 was significantly higher at a dose of 400 μl (p<0.05), and the expression of α-SMA and collagen was found to be lower significantly in the treatment group than the control group.. Conclusion: HMSCS may be a therapy for peripheral ischemia with diabetes by increasing angiogenesis and increasing the expression of angiogenic factor genes, especially TSP-4 in DM with HLI.