A pre -treatment step could help transplant pancreatic islands more survive in patients with type 1 diabetes, according to a new preclinical study by Weill Cornell Medicine researchers. A combination of small molecules expanded the lives of cells to female mice and adding two molecules to the mixture the survival of the cells in male mice.
The findings published on June 24 Cellular cellIt could allow doctors to cure more patients with fewer cells.
In type 1 diabetes, autoimmune cells attack the pancreatic islets, destroying beta insulin cells and letting patients depend on insulin injections. The current transplant process approved by the FDA replaces these cells with pancreatic islet cells by one or more deceased organ donors. It usually takes up to 48 hours to isolate islands from the donor to injection into a vein that carries them to the recipient’s liver. Once in the liver, islet cells begin to produce insulin, as in a healthy pancreas.
However, many transplanted cells die shortly after the procedure and the complications may result from the targeting of the liver. Cell transplantation under the skin, a choice with some potential advantages, also has challenges with dead cells. Dr. Shuibing Chen, Professor of Kilts Family Surgery and Director of the Health Genom Center at Weill Cornell Medicine, noted research by others showing that the pre -treatment of one type of cells used to replenish blood cell populations during a period Approach to islands cells.
“With our new strategy, we should only need one donor per patient or maybe a donor could contribute cells to two patients, reducing waiting time for patients to receive treatment,” said Dr. Chen, who is also a member of the Hartman Institute for therapeutic Body.
Small molecule
Determination of the best pre-treatment approach typically requires several expensive and intense drug screens, but J. Jeya Vandana, a postgraduate student in the Tri-Incidential Doctoral Program in Chemical Biology and the first writer of the document, had an idea. “Jeya combined chemical screens with a RNA cell sequence technology so that we can control multiple readings in an experiment,” Dr. Chen said.
With their system, which they call Chemperturb-Seq, each cell in an experiment receives a unique bar code and is treated for 48 hours with a unique small molecule. After treatment, the group concentrates RNA cells and sequences. The linear code tells the researchers that cells responded well to a particular molecule. All data is publicly available through a website called ChemperturbdB, powered by an artificial intelligence assistant that is similar to Chatgpt.
Sex differences
The execution of Chemperturb-Seq with a human beta cell line led to the discovery of a pre-treatment called lips. This combination of beta-lipotropin, insulin-1 growth factor, and prostaglandin E2 enhanced the survival of beta cells and human islands by donors when transplanted subcutaneously into a model of type 1 mouse diabetes compared to witnesses. But there was a catch.
Jeya was transplanted for the first time into female mice and the approach worked very well, but when transplanting pre -treatment cells into male mice, it failed. “
Dr. Shuibing Chen, Professor of Kilts Family Surgery and Director of the Health Genom Center at Weill Cornell Medicine
Returning to the drawing, the team used the Chemperturb-Seq to predict other small molecules that could help cells live longer in males. The result was a cocktail called Liphs, which included the three lip molecules and histamine and serotonin, which were successful in males.
Armed with their new technique, Dr. Chen will conduct more studies to determine if the results maintain additional preclinical models. The team also adds even more small molecule data to the site.
Source:
Magazine report:
Vandana, JJ, et al. (2025). The Chemperturb-Seq display identifies a small molecule cocktail that enhances the survival of human beta cells after subcutaneous transplantation. Cellular cell. doi.org/10.1016/j.stem.2025.06.002.
