A new landmark study shows that gene-editing blood stem cells, or treating them with a triad of immune cell therapies, can reverse type 1 diabetes in mice.
Edited blood stem cells may be used to re-educate the immune system’s T cells, thereby curbing uncontrolled immunity in type 1 diabetes.
Blood stem cells from humans and mice with diabetes have a genetic defect that reduces their capacity to produce enough of a T cell-blocking protein called PD-L1.
PD-L1 is already being studied for use against many types of cancer and for the regulation of a number of autoimmune diseases.
At a cellular level, the job of PD-L1 is to detect and bind to proliferating, autoreactive T cells through a receptor on their surface called PD-1.
Once in contact with the protein PD-L1, PD-1 acts like an “off’ switch and basically tells the T cells to leave the insulin-producing cells alone.
In the new study, researchers at Boston Children’s Hospital have found that it is possible to engineer the cells using two different methods to get them to make more PD-L1.
The first method used for regenerating blood stem cells was gene editing. Researchers simply replaced the defective copy of the gene that controls the production of PD-L1 with a normal one via a harmless virus.
The second technique consisted of treating the blood stem cells with three molecules used in immune cell-based therapies targeting multiple sclerosis (MS) and cancer: interferon beta, interferon gamma and polyinosinic-polycytidylic acid.
Following treatment, the blood stem cells directly homed to the pancreas. In stem cell science, “homing” refers to the stem cells’ ability to find their destinatio, or site of action, and increases the success of cell-based therapies.
In both experiments, the treated blood stem cells reversed diabetes in almost all the mice in the short term, and a third of them stayed diabetes-free for the rest of their lives. The stem cells also inhibited human autoimmune responses in vitro.
Researchers are still trying to determine how long the modified blood stem cells can remain active in the body for before a repeat treatment becomes necessary. A pill is being developed to modulate blood stem cells like these interventions do.
While previous research focused on increasing the numbers of blood stem cells in patients, these findings suggest that addressing their problematic genetic defect that causes too little PD-L1 may be a better strategy in type 1 diabetes.
The findings were published in the journal Science Translational Medicine.

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