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The Research Of Using Menstural Blood Progenitor Cells In Type1Diabetes

Posted on:2015-02-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:X X WuFull Text:PDF
GTID:1264330428483248Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Menstrual blood progenitor cells (MBPCs) have attracted much attention in the area of regenerative medicine because of their various properties such as easy collection, broader plasticity, faster proliferative rate, immunoregulation and secreting multiple factors. Although a growing body of research suggests that MBPCs have great application potentials in tissue repair and various disease treatments, their theraputic effect in Type1diabetes (T1D) has not been studied. In this study, we mainly discuss cytological properties of MBPCs and their ability in promoting β cell regeneration and in vitro inducing MBPCs into β cell.Firstly, our study indicated that MBPCs directly transplanted into T1D mice could effectively reduce glucose, maintain weight, prolong lifespan and increase serum insulin. Pathological observation and immunohistochemistry analysis showed that MPBCs could maintain normal structure of βcell and increase βcell number. In vivo cell tracking found MBPCs could migrate to damaged pancreas and locate to islet, duct and pancreatic exocrine structures. Immunofluorescence assay indicated that MBPCs could not differentiate into insulin producing cells (IPCs) but could promote Ngn3expression. Ngn3is a marker of β precursor cell.Its activation represents the formation of βcell in embryonic pattern. Further study showed that Ngn3+cells exist not only in duct epithelial cells but also in islet and pancreatic exocrine structures, which indicated MBPCs could activate both duct precursor cells and other pancreatic stem cells differentiation. To further prove MBPCs promoted differentiation of endogenous stem cells, we detected a series of genes relative to β cell formation. Compared to T1D mice and normal mice, these genes in MBPCs were up-regulation expression. From these results, we concluded that MBPCs could improve hyperglycemia of T1D mice through promoting differentiation of endogenous stem cells.We also studied the ability of MBPCs being induced to β cell in vitro. Inducible factors associated with pancreatic differentiation including Activin A, RA, EGF, FGF10, indolactim V and Exendin-4were used in a step-by-setp and combination manner to induce MBPCs. The induced cells could express MafA (marker gene of mature βcell), secret insulin in response to high concentration of glucose and insulin antibody staining is positive. These results indicate that induced cells have characteristics of β cells and MBPCs have the ability of being induced to β cells.
Keywords/Search Tags:human menstrual blood, β cell regeneration, Type1disease, insulin-producing cells (IPCs), transplantion, induction
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