Micro-Patterned Substrates for Differentiating Mesenchymal Stem Cells into Insulin Producing Cells



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Conventional insulin therapy for Type 1 diabetes mellitus is often accompanied by long-term complications such as heart disease and kidney damage, if patients do not follow a very strict and controlled regime of taking insulin shots. Transplantation of pancreatic islets is a therapeutic option available for Type 1 Diabetes, where in donor islets are transplanted into patients for controlling glucose levels without the need of insulin shots. Although the current islet transplantation Edmonton protocol has made progress in successfully treating diabetic patients, a lack of viable donor cells and side effects associated with immunosuppressant drugs make alternative therapeutic options critical. Cell replacement therapy via differentiation of adult stem cells into glucose-responsive insulin producing cells (IPCs) has recently provided hope for Type I diabetes. However, inadequate functional performance of the differentiated cells with poor long-term insulin production has slowed further progress. Thus, there is a critical need for improving the total yield of differentiated cells and their functional performance. In this study we investigated the potential of a novel substrate of micro-patterned Titanium diboride (TiB2) on Silicon (Si) wafers for culturing adult human bone marrow mesenchymal stem cells (hBM-MSCs) and differentiating them into insulin producing cells (IPCs). The hypothesis is that these substrates enable formation of aggregates, thereby enabling a 3D micro-environment for differentiation. Stereomicroscopy showed MSCs preference for TiB2 patterns over Si and the formation of uniform aggregates only on the TiB2 after the differentiation protocol. Moreover, MSCs not only remained at 80% or more viable when aggregated, but phenotyping analysis for the presence of biomarker CD105 demonstrated conserved multi-lineage potential throughout the 9 day pre-differentiation incubation period. More importantly, our results suggest a 2-3 fold increase of insulin secretion from MSCs differentiated on the micro-patterned substrates when compared against differentiation in conventional tissue culture flasks.



Mesenchymal stem cells, Insulin producing cells, BioMEMS, Substrate, Durotaxis