Stem cells from cord blood “re-educated” the immune system T cells of people with type 1 diabetes so their pancreas started producing insulin again, thereby reducing the amount of insulin they needed to inject. These are the findings of a study led by Dr Yong Zhao, from University of Illinois at Chicago that were published online on Tuesday in the open access journal BMC Medicine.
Type 1 diabetes develops when the body’s own immune system attacks and destroys the insulin-producing islet beta cells in the pancreas. As a result, the body can’t make insulin, causing blood glucose to reach dangerous levels and damage all the organs in the body.
In their background information, the researchers note that tests on mice and cells of patients with diabetes have shown that multipotent cells derived from cord blood “can control autoimmune responses by altering regulatory T cells (Tregs) and human islet beta cell-specific T cell clones”.
Cord blood is blood that is collected from the placenta and umbilical cord after childbirth. It is a rich source of stem cells that can treat a range of blood and genetic disorders.
In their paper the researchers describe how they developed a procedure they called “Stem Cell Educator therapy” where the diabetic patient’s blood is circulated through a closed-loop system that separates lymphocytes (a class of immune cell that includes T cells) from the whole blood and co-cultures them with cord blood stem cells from healthy donors for two to three hours before returning the “re-educated lymphocytes” to the patient’s circulation.
For this small, open-label, phase1/phase 2 study they recruited 15 patients with type 1 diabetes aged from 15 to 41 years (median 29) with a diabetic history ranging from 1 to 21 years (median 8).
All but three of the patients (the controls) underwent Stem Cell Educator therapy once. The controls underwent a sham treatment where they received no educated cells.
The researchers checked the patients’ progress 4, 12, 24 and 40 weeks after therapy. Six of the patients who had the therapy had some residual beta cell function (moderate type 1 diabetes) and the other six had no residual beta cell function (severe type 1 diabetes).
The results showed that the median daily dose of required insulin was down by 38% at week 12 for the six patients with moderate diabetes and by 25% for the patients with severe diabetes. There was no change in required insulin dose for the controls.
All the patients who had received the Stem Cell Educator therapy also showed improved levels of C-peptide, a biomarker used to measure how well beta cells are working (it is a protein fragment that is left behind when insulin is made in the pancreas).
Levels of C-peptide continued to improve at 24 weeks and was maintained to the end of the study (at 40 weeks).
Zhao told the press:
“We also saw an improved autoimmune control in these patients. Stem Cell Educator therapy increased the percentage of regulatory T lymphocytes in the blood of people in the treatment group. Other markers of immune function, such as TGF-beta1 also improved.”
The researchers detail the improvements in immune function in their paper:
“Individuals who received Stem Cell Educator therapy exhibited increased expression of costimulating molecules (specifically, CD28 and ICOS), increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance.”
Zhao suggests the autoimmune regulator AIRE in the cord blood stem cells mediated these changes which in turn allowed the pancreatic islet beta cells to recover.
Written by Catharine Paddock PhD