Researchers have made a major breakthrough in the process of developing a stem cell therapy for the treatment of Type 1 diabetes.
Scientists from the Salk Institute, USA, are developing an approach to treat Type 1 diabetes, which occurs when the pancreas cannot produce enough insulin to control glucose levels in the blood. The researchers are currently working on using stem cells to create insulin-producing cells (called beta cells) that could replace non-functional pancreatic cells.
The results of the study were published in the journal Nature Communications.
The scientists have developed a new way to create beta cells, and investigated their efficacy using a mouse model of Type 1 diabetes. They found that the animals’ blood sugar was brought under control within about two weeks.
Salk Professor Juan Carlos Izpisua Belmonte, the paper’s senior author, said: “Stem cells are an extremely promising approach for developing many cell therapies, including better treatments for Type 1 diabetes. This method for manufacturing large numbers of safe and functional beta cells is an important step forward.”
In the current work, the investigators started with human pluripotent stem cells (hPSCs). These cells, which can be derived from adult tissues (most often the skin), have the potential to become any kind of cell found in the adult body. Using various growth factors and chemicals, the investigators coaxed hPSCs into beta cells in a stepwise fashion that mirrored pancreatic development.
Producing beta cells from hPSCs in the lab is not a new approach, but in the past the yields of these cells have been low. With existing methods, only about 10% to 40% of cells become beta cells. By comparison, techniques used to create nerve cells from hPSCs have yields of about 80%. Another issue is that, if undifferentiated cells are left in the mix, they could eventually turn into another kind of cell that would be unwanted.
Co-first author Haisong Liu, a former member of the Belmonte lab, said: “In order for beta cell-based treatments to eventually become a viable option for patients, it’s important to make these cells easier to manufacture. We need to find a way to optimize the process.”
To address the problem, the researchers took a stepwise approach to create beta cells. They identified several chemicals that are important for inducing hPSCs to become more specialised cells, including chemicals that resulted in beta cell yields of up to 80%. They also looked at the ways in which these cells are grown in the lab.
Three-dimensional cell growth
Co-first author Ronghui Li, a postdoctoral fellow in the Belmonte lab, said: “Normally cells are grown on a flat plate, but we allowed them to grow in three dimensions.”
Growing the cells in this way creates more shared surface area between the cells and allows them to influence each other, just as they would during human development.
After the cells were created, they were transplanted into a mouse model of Type 1 diabetes. The model mice had a modified immune system that would not reject transplanted human cells.
Co-first author Hsin-Kai Liao, a staff researcher in the Belmonte lab, said: “We found that, within two weeks, these mice had a reduction of their high blood sugar level into normal range.
“The transplanted hPSC-derived beta cells were biologically functional.”
The researchers will continue to study this technique in the lab to further optimise the production of beta cells. More research is needed to assess safety issues before clinical trials can be initiated in humans. The investigators say the methods reported in this paper may also be useful for developing specialised cells to treat other diseases.