Single-gene edits fail to protect transplanted insulin-producing cells
In people with type 1 diabetes, the immune system mistakenly destroys the pancreatic beta cells responsible for producing insulin. Patients therefore require lifelong insulin therapy to regulate their blood glucose levels.
Researchers from Koç University explored whether editing a single gene could help transplanted insulin-producing cells survive immune attack. They focused on two genes, RNLS and HIVEP2, believed to protect beta cells from autoimmune destruction. Utilizing CRISPR-Cas9 technology, they disabled each gene in mouse and human beta-cell lines and tested the impact on the cells' ability to respond to glucose and produce insulin.
While HIVEP2 loss did not significantly affect beta-cell function, losing RNLS led to a slight drop in insulin production in mouse cells. After transplanting the edited beta-cell spheroids under mouse or human skin, researchers monitored them using bioluminescence imaging. The study found that neither gene disruption prolonged graft survival.
Both edited cells were rejected at similar rates compared to unedited control cells, with human grafts being eliminated more quickly. Although these genes may play a role in specific autoimmune or cellular stress pathways, the research shows that altering a single gene is not enough to shield beta-cell grafts from the complex immune responses involved in transplant rejection.
The findings suggest that effective protection may necessitate a combination of genetic modifications or the use of gene editing alongside immunomodulatory biomaterials.
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