Permanent acceptance of organ transplants requires “immune tolerance,” and studies have suggested that hematopoietic stem cells (HSCs, blood-forming cells in the bone marrow) may play a role in tolerance induction.
Daniel Moore, M.D., Ph.D., and colleagues have now demonstrated that mobilization of HSCs is required for transplantation tolerance in a mouse model of type 1 diabetes – and that HSC activity depends on a functioning sympathetic nervous system. Disruption of either HSC mobilization or the sympathetic nervous system resulted in failure of tolerance to transplants of insulin-producing pancreatic islets.
The investigators found that excess expression of the receptor CXCR4 held HSCs in the bone marrow, and that blocking this receptor mobilized HSCs and prolonged islet transplant survival.
The findings, reported in the journal Diabetes, show that HSCs play a role in establishing immune tolerance and suggest that understanding the stem cell response to immune therapies for type 1 diabetes may help maximize the effectiveness of those interventions.
This research was supported by the National Institutes of Health (grants DK090146, DK097410, DK107321, GM007347, GM008554), Juvenile Diabetes Research Foundation, Turner Hazinski Scholars Award, Alice and Henry Hooker Diabetes Research Scholar Award, Price Family Discovery Award, and Merz Family Scholar Award in Transplantation.
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