At the Joslin Diabetes Center, a team of researchers have found an uncommon strategy which may potentially help to protect the transplanted beta cells to slow the original onset of type 1 diabetes, where person’s own immune cells start to attack its own insulin-producing beta cells in the pancreas. The study was published in Nature Metabolism.
In the past, researchers have investigated the large volumes of replacement beta cells, and they are still trying to investigate the suitable options to guard these cells against the immune attack.
— BioNews Central (@bionewscentral) July 27, 2020
Source: JDRF and Diabetes Statistics
Previously, research conducted on mouse models and in human cells elucidated that targeting a protein called renalase may considerably protect the pancreatic beta cells against the potential autoimmune attack. It does by strengthening them against stress, according to Stephan Kissler, an investigator in Joslin’s Section on Immunobiology, associate professor of medicine at Harvard Medical School, and co-senior author on a paper describing the work in Nature Metabolism. He along with his team also proved that one of the existing FDA-approved drug sign ificantly inhibits renalase protein and increases the survival of beta cells in those lab models.
The current study also indicates that there is a growing evidence that functional problems of pancreatic beta cells may also act as the one of the causing factor triggering the autoimmune attack in type 1 diabetes, say Kissler and Yi, who is an assistant investigator in the Islet Cell and Regenerative Biology Section.
“You might have genes that make the beta cell a little bit dysfunctional and more prone to becoming a target of the immune system,” says Kissler.
The current research started by investigating the potential ways to protect beta cells from autoimmune attack by inhibiting the required genes across the genome, one at a time, to find the potential mutations that could protect the beta cells, using a screening technique based on the CRISPR gene-editing method with a beta cell line from a “non-obese diabetic” (NOD) mouse that models type 1 diabetes. The CRISPR screen for surviving beta cells produced the gene for renalase, which reconfirm the previous research associated with type 1 diabetes. Following, they created the NOD mouse beta cells and transplanted these cells to NOD mice with autoimmune diabetes.
The researcher then investigated further to determine if the cells lacking the renalase gene caused a diminished response from T immune cells in a dish. It was found that one type of T cell was less likely to attack these knockout cells than to attack normal beta cells. Then they studied it further under Endoplasmic reticulum ER stress. To control this ER stress, they used the FDA approved pargyline drug in their mouse transplant model, then the Joslin researchers found that the drug protected beta cells extremely well.
Kissler further added about the drug, saying, “Since it’s FDA-approved and the drug is safe, this would be the best approach to test if the protection we observed in mice and human cells will hold true in people.”