Abstract
BackgroundAlthough diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats.MethodsMSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly.ResultsHuman nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver.ConclusionThus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.
Highlights
Diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique
Gene expression in the differentiated cells To determine whether the mesenchymal stem cells (MSCs) had differentiated into insulin-producing cells, the expression of genes involved in pancreatic β-cell development and insulin production was examined by reverse transcriptase-polymerase chain reaction (PCR) and real-time PCR
Detection of C-peptide in the differentiated cells derived from mesenchymal stem cells from the umbilical cord Anti-human C-peptide antibodies revealed that C-peptide was expressed in undifferentiated MSCs and differentiated IPCs
Summary
Diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Mesenchymal stem cells (MSCs) were first isolated from bone marrow [9] and have the potential to differentiate in culture into muscle cells, adipocytes, osteocytes, chondrocytes [10,11,12], cardiomyocytes [13,14,15,16] and pancreatic β cells [17]. Insulin-producing cells can be developed from bone marrow MSCs [23], adipose tissue-derived stem cells [24], and human umbilical cord blood-derived mononuclear cells [25], the number of MSCs that can be cost-effectively isolated and differentiated remains a major limitation. Because MSCs from the umbilical cord can be isolated and expanded in culture, they may provide a novel source of cells for cellular type 1 DM therapies
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