VANCOUVER – A new stem cell transplant approach addressed both underlying autoimmunity and pancreatic beta-cell repair and regeneration in a pilot study of patients with established type 1 diabetes mellitus.
In an open-label, randomized, controlled trial of 42 patients, cotransplantation of umbilical cord mesenchymal stromal cells and autologous bone marrow mononuclear cells, without any immunotherapy, was tested against usual care.
Susan London/Frontline Medical News
Xiumin Xu
At 1 year, the area under the curve for C-peptide during an oral glucose tolerance test had more than doubled among the transplant recipients, whereas it had fallen among those managed with usual care, presenting author Xiumin Xu reported at the World Diabetes Congress. The transplant group also saw greater improvements in other metabolic measures, in immune indicators, and in scores for mental well-being and quality of life.
Overall, the transplant procedure was safe and well tolerated, she reported. Severe hypoglycemic events were less common in the transplant group. One patient had transient abdominal pain during the procedure, and another had bleeding at the site where the infusion catheter was placed.
“Although the absolute change in C-peptide is marginal, it is relatively significant in view of the long disease duration,” commented Ms. Xu, a researcher with the Diabetes Research Institute, Cell Transplant Center, University of Miami; The Cure Alliance, Miami; and the Diabetes Research Institute Federation in Hollywood, Fla.
The trial was unusual in enrolling patients with established diabetes, Ms. Xu pointed out. Most type 1 diabetes studies have enrolled patients with recent disease onset, but increasing evidence suggests some preservation of beta-cell mass and C-peptide production in those with established disease.
The researchers tapped mesenchymal cells for transplant because of their known ability to modulate immune response and tissue repair through paracrine mechanisms. In a preclinical model of diabetes, combining these cells with bone marrow cells synergistically improved glycemia and insulin levels (Stem Cells. 2008;26:244-53).
The trial, conducted in China, enrolled patients 18-40 years old who had type 1 diabetes for at least 2 years and were otherwise generally healthy. They were required to have a hemoglobin A1c level of 7.5%-10.5%, a fasting serum C-peptide level of less than 0.1 pmol/mL, and a daily insulin requirement of less than 100 IU.
The transplant group underwent sequential infusion of autologous bone marrow cells and umbilical cord mesenchymal stromal cells over 30 minutes through supraselective pancreatic artery cannulation. The control group continued to receive usual clinical care.
Trial results, reported at the congress and recently published (Diabetes Care January 2016. 39[1]:149-157), showed that transplant recipients, compared with their usual care counterparts, had improvements in the area under the curve for C-peptide (+105.7% vs. –7.7%, P = .013), the trial’s primary endpoint.
They also had improvements in the area under the curve for insulin (+49.3% vs. –5.7%, P = .027), hemoglobin A1c (–12.6% vs. +1.2%, P less than .01), fasting blood glucose (–24.4% vs. –4.3%, P less than .05), and daily insulin requirements (–29.2% vs. 0%, P less than .01).
“Although metabolic control improved in patients receiving stem cell transplant, insulin independence was not achieved,” noted Ms. Xu, who disclosed that she had no relevant conflicts of interest.
The transplant group also had more favorable changes in markers of immune function, such as an increase in interleukin-10 levels and a decrease in serum interferon-gamma levels.
Additionally, they had significant improvements in scores for anxiety, depression, and quality of life relative to their usual care peers.