Objective
Our objective is to test a specific type of automated culture system, ‘a bioreactor’, which is widely used by the industry to produce vaccines or other types of therapeutics, and has recently been adapted for the culture of human cells. These systems allow for careful monitoring and adjustment of important conditions like acidity (pH), oxygen levels, and temperature, and are expected to make an impact on our capacity to produce a very large number of stem cell-derived insulin-producing cells, ultimately for islet replacement therapy.
Background Rationale
Stem cells can be converted to insulin-producing cells. Although first clinical steps have been made and show exciting results, the sustainability of this type of stem cell-based therapy in the future will require major new developments on specific aspects, including the capacity of scientists to produce very large numbers of these so-called stem cell islets in a robust and ultimately cost-effective manner.
Description of Project
Type 1 Diabetes (T1D) is a chronic disease characterized by the specific destruction of the insulin-producing cells by the immune system. Currently, there is no cure for T1D. Yet, a functional cure can be achieved by transplanting insulin-producing cells from organ donors to help stabilize blood sugar levels without causing harmful low blood sugar episodes. However, the number of donor organs is very limited, so an alternative source of insulin-producing cells is needed.
An attractive option is to grow new insulin-producing cells from stem cells. These so-called pluripotent stem cells (PSC) can be converted into any cell type of the body. When instructed properly with specific molecules, these cells can become lab-grown versions of pancreatic islets, producing insulin. Exciting progress has been made with early clinical studies showing that these ‘stem cell islets’ can help manage blood sugar in patients with type 1 diabetes. Yet, numerous challenges remain before this kind of therapy can become a widespread treatment.
Generating stem cell-derived islets is a complex and fragile process, with potentially unwanted cell types present in the end product, and large-scale production representing a major challenge. Here, we propose combining an automated bioreactor production system with an enrichment method we developed recently to make a better SC islet product, and ultimately contribute to making this cell therapy more widely available and more sustainable in the future.
Anticipated Outcome
If successful, this project will lead to a novel method to generate a large number of stem cell-islets. The unique aspect of our proposal is that our laboratory has already engaged in the translation of research-grade methods to clinical-grade methods. Furthermore, we have access to a special facility to make cell products for patients, and all the expertise required to reach this stage.
Relevance to T1D
* General Audience Summary - Relevance to Type 1 Diabetes
Type 1 diabetes results from the selective destruction of insulin-producing cells by the immune system. Unlike skin cells, for instance, the regeneration of beta-cells does not occur in humans. Recent studies revealed that lab-grown insulin-producing cells made from stem cells can provide a functional cure to patients transplanted with these cells. However, several challenges remain before this type of therapy can be made available to many patients. One of them is the need to improve the method to upgrade the production of these stem cell islets. This is the challenge we are addressing in the current project proposal.