Project Title:

Directed differentiation of embryonic stem cells to insulin producing cells as a cure for Type 1 diabetes.

Discipline:

Cell and Molecular Biology

Chief Investigator:

Associate Professor Mark Nottle

Funding Amount:

$74,882

Recipient:

The University of Adelaide

Overview:

The directed differentiation of human embryonic stem cells to insulin producing cells is seen as a cure for Type I diabetes. However human ESCs are not the same as those originally isolated in mice which has led to the suggestion that these may not be the best cell type for this therapy. We have developed a method which allows us to isolate ESCs similar to that originally isolated in mice. In characterising these cells we have shown that these can be directed to differentiate to insulin producing cells. The aim of the present study is to complete the characterization of these cells.

Research Outcomes:

Researchers:

Mark Nottle, Toby Coates, Darling Rojas-Canales, Ivan Vassiliev

Research Completed:

2018

Research Findings:

The directed differentiation of human embryonic stem cells to insulin producing cells is seen as a cure for Type 1 diabetes. However, human ESCs are not the same as those originally isolated in mice, which has led to the suggestion that these may not be the best cell type for this therapy. We have developed a method which allows us to isolate ESCs similar to that originally isolate in mice. In characterising these cells we have shown that these can be directed to differentiate to insulin producing cells. The aim of the present study was to further characterise these cells in vitro and demonstrate that they can restore glucose homeostasis in a diabetic mouse model. The major finding from this study was that although around half our cells are insulin producing cells we also found cells which were similar to the other two major cell types found in the islet suggesting that our differentiation protocol produces cell clusters which are similar to islets which may provide a more effective treatment for Type 1 diabetes than just transplanting insulin producing cells.

Key Outcomes:

The directed differentiation of human embryonic stem cells to insulin producing cells is seen as a cure for Type 1 diabetes. However, human ESCs are not the same as those originally isolated in mice, which has led to the suggestion that these may not be the best cell type for this therapy. We have developed a method which allows us to isolate ESCs similar to that originally isolate in mice. In characterising these cells we have shown that these can be directed to differentiate to insulin producing cells. The aim of the present study is to complete the characterisation of these cells.

Background

Type 1 diabetes affects 1 in 250–350 people by the age of 20 years. Replacement therapy with insulin sustains many millions of people but fails to restore normal glucose homeostasis. It therefore reduces but does not abolish the risk of late microvascular and macrovascular complications of diabetes. The aim of the present study  is to complete the characterisation of insulin producing cells derived from a new embryonic cell type isolated by us as a potential cell therapy for Type 1 diabetes (T1D). In particular we propose to;

  1. Complete the in vitro characterisation these cells in terms of insulin and pancreatic hormone production.
  2. Demonstrate these cells can be used to restore glucose homeostasis in a diabetic mouse model.

Progress

  1. Complete the in vitro characterisation these cells in terms of insulin and pancreatic hormone production.

Further characterisation of these cells were undertaken. The results from this study showed that while our cells were predominantly insulin producing cells we also found cells which were similar to alpha and delta cells suggesting that our differentiation protocol produces cell clusters containing all three major cell types found in the islet. Which may provide a more effective treatment for Type 1 diabetes than just transplanting insulin producing cells.

  1. Demonstrate these cells can be used to restore glucose homeostasis in a diabetic mouse mode

This work was delayed because of

  1. Major technical problems in producing mouse feeder layers which we culture our ESCs on.
  2. Shifting our laboratory from to the new AHMS building in June/July which require our lab to be shut down for 2 months.
  3. Dr Vassiliev suffering from health issues in the second half of the year.

Current status and future work

All three hurdles have now been overcome and we expect to complete Aim 2 in the first half of the year having attracted further funding to complete this work. Furthermore as a result of this work we are currently negotiating with two companies to isolate our stem cell type in humans.

Research Papers:

Related Publications:

Future Outcomes:

As a result of this work, the Grant recipient is currently negotiating with two companies to isolate its stem cell type in humans.

Remarks:

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