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Type of publication: Baccalaureate Thesis
Type of document:

Year: 2010

Authors: Theiler, Anna

Title: Engineering mesenchymal stem cell for insulin secretion.

Source: Bakkalaureatsarbeit, Vet. Med. Univ. Wien, pp. 45.


Advisor(s):

Klein Dieter

Reviewer(s):
Egerbacher Monika

Vetmed Research Units:
Institute of Virology


Abstract:
Type 1 diabetes mellitus is an endocrine disease, which is characterised by the specific destruction of the insulin producing cells in the pancreas. The lack of insulin results in hyperglycaemia and is accompanied by specific symptoms such as polydipsia, polyuria and weight loss. Currently about 2 million people suffer from type 1 diabetes mellitus in Europe and Northern America and the amount is increasing. At present, no therapy is available to cure type 1 diabetes mellitus. Therefore, affected people are treated with human recombinant insulin. Islet transplantation might display an alternative treatment, but this possibility is limited by the scarcity of allogeneic donor islets and beside that, treatment with severe immunosuppressive drugs is required. Therefore, in vitro engineering of insulin producing cells might display an appropriate approach in type 1 diabetes treatment. Mesenchymal stem cells (MSCs) are able to differentiate into mesodermal cell lineages but also into neuroectoderm, visceral mesoderm and endoderm under specific experimental conditions. In addition, MSCs are thought to have great potential to differentiate into insulin producing phenotypes by stimulation with specific growth factors. In this study, insulin inducing agents were used to generate insulin producing cells from four hMSC donors. Cells from 2 of 4 donors showed morphological changes in structure and shape. Moreover, changes in mRNA gene-expression pattern of genes related with [beta]-cell development were measured by real-time RT-PCR. We could not detect mRNA expression of genes, specific for insulin producing phenotypes in these cells but islet-like structures stained positive with dithizone, which might indicate the presence of insulin. Interestingly, it was possible to detect insulin in cells from one donor after glucose stimulation. This promising result showed that these engineered cells were able to respond to glucose stimulation in principle. However, the differentiation protocol needs to be optimized for a more efficient generation of insulin producing cells from hMSCs.


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