Stories about: Paolo Fiorina

Pre-treated blood stem cells reverse type 1 diabetes in mice

autoimmune attack in type 1 diabetes
In type 1 diabetes, autoreactive T-cells (like the one in yellow) attack insulin-producing beta cells in the pancreas. What if blood stem cells could be taught to neutralize them? (Image: Andrea Panigada)

Type 1 diabetes is caused by an immune attack on the pancreatic beta cells that produce insulin. To curb the attack, some researchers have tried rebooting patients’ immune systems with an autologous bone-marrow transplant, infusing them with their own blood stem cells. But this method has had only partial success.

New research in today’s Science Translational Medicine suggests a reason why.

“We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease,” says Paolo Fiorina, MD, PhD, of Boston Children’s Hospital, senior investigator on the study.

But they also found that the defect can be fixed — by pre-treating the blood stem cells with small molecules or with gene therapy, to get them to make more of a protein called PD-L1.

In experiments, the treated stem cells homed to the pancreas and reversed hyperglycemia in diabetic mice, curing almost all of them of diabetes in the short term. One third maintained normal blood sugar levels for the duration of their lives.

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Rescuing intestinal stem cells from attack in diabetes

diabetic enteropathy and colonic stem cells
Blood levels of the hormone IGFBP3 (enterostaminine), shown here in green, are markedly elevated in people with longstanding type 1 diabetes and launch a lethal attack on intestinal stem cells. Adding a protein that soaks up the excess hormone restores normal stem cell function and could help prevent or treat diabetic enteropathy. (All images by Riseon)

Up to 80 percent of people with long-standing type 1 diabetes develop gastrointestinal symptoms—abdominal pain, bloating, nausea, vomiting, diarrhea, constipation and fecal incontinence—that severely diminish quality of life. Recent evidence suggests that this condition, known as diabetic enteropathy, results from damage to the intestinal lining, but the details beyond that have been unclear.

A study in this week’s Cell Stem Cell, led by Paolo Fiorina, MD, PhD, now provides some answers. It demonstrates how diabetes can lead to destruction of the stem cells that maintain the intestinal lining, and identifies a potential drug that could protect these stem cells and prevent or treat diabetic enteropathy.

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