| Summary: | 博士 === 國立陽明大學 === 臨床醫學研究所 === 103 === Mesenchymal stem cells (MSCs) are multipotent adult stem cells harboring a wide range of differentiations and leukocyte antigen-restricted immunosuppressive properties that lead to an increasing use of MSCs in immunomodulation and in regenerative medicine. In recent years, our research team focused on the study of regeneration medicine for diabetes mellitus. We generated insulin-producing cells (IPCs) from stem cells in human tissues including Wharton’s jelly, surgical resected pancreatic tissue, and bone marrow. Transplantation of these functional cells into diabetic mice could decrease blood glucose level. Therefore, they are potential sources of cell therapy for diabetic patients. Because Wharton’s jelly MSCs (WJ-MSCs) can be easily isolated and expanded in vitro, these cells are thought to be an optimal source of cells for cellular therapies to improve diabetes. The specific results of my study are first, I improved the culture condition of WJ-MSCs which could generate large quantity of functional IPCs. The differentiation condition was modified, and the characteristics of differentiated islet-like cell aggregates could be determined by immunocytochemical staining, real time PCR, ELISA and glucose challenge test. Second, I found a Port-A catheter could be used to transplant IPCs differentiated from human WJ-MSCs into the portal vein to alleviate hyperglycemia among streptozotocin-induced diabetic rats. IPCs containing human C-peptide and human nuclei were detected in the liver of rat by immunohistochemistry stain. Third, WJ-MSC-GFP-treated NOD mice had significantly lower blood glucose level and higher survival rates than saline-treated mice. Systemic and local levels of autoaggressive T cells, including T helper 1 cells and IL-17-producing T cells, were reduced and regulatory T cell levels were increased after WJ-MSC-GFP-treatment. Anti-inflammatory cytokine levels were also increased and dendritic cells were decreased. Furthermore, IPCs differentiated from WJ-MSCs-GFP were detected in the pancreas of mice by colocalization of human C-peptide and GFP. Additionally, significantly more intact islets and less severe insulitis were found. Thus, I concluded that undifferentiated WJ-MSCs could ameliorate diabetes by both differentiating into IPCs in vivo with immunomodulatory effects and repairing the destroyed islets in NOD mice. My study results will provide basic and essential information for future application of cell regenerative therapy in diabetic patients.
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