Therapy using the patient's lymphocytes passed through a device with cord blood stem cells may "educate" the patient's cells to provide safe, lasting treatment for patients with type 1 diabetes, according to the results of a small Chinese study.
Those patients with moderate diabetes and some residual beta cell function (Group A) exhibited improved fasting C-peptide levels at 12 and 24 weeks post-treatment, Yong Zhao, PhD, of the University of Illinois at Chicago, and colleagues reported online in BMC Medicine.
Patients with more severe disease and no residual beta cell function (Group B) also showed improvement at every follow-up.
Treatment consisted of passing lymphocytes from the patient's blood through discs containing adherent multipotent cord blood stem cells. After two or three hours, the lymphocytes were collected and returned to the patient.
No participants suffered any serious adverse events, reporting only mild discomfort during venipuncture and apheresis, which resolved at the conclusion of the procedure. There were also no significant differences at 24 hours after treatment in white blood cell counts or body temperature.
In the phase I/II open-label trial, the researchers enrolled 15 patients with type 1 diabetes (mean duration 8.5 ± 6.4 years) receiving care at the General Hospital of the Jinan Military District. Patients were enrolled if they met the 2010 diagnosis criteria of the American Diabetes Association and blood tests found at least one autoantibody to pancreatic islet beta cells.
Exclusion criteria included liver, kidney, or heart disease, pregnancy, use of immunosuppressive medications, viral diseases, or immunodeficiency diseases. After two days of hospitalization to monitor early adverse reactions, follow-ups were scheduled at 4, 12, 24, 40 weeks after treatment.
Twelve patients were divided into two groups of six according to the severity of their diabetes and whether they had any residual beta cell function. Both cohorts were given full treatments. A third group of three individuals was given a single sham treatment to serve as a process-control.
Addressing the autoimmunity that underlies type 1 diabetes has been a major impediment to using stem cells for long-term treatment. Studies in mice have shown that cord blood stem cells can be used to alter immune function and they have been shown to modulate the immune function of type 1 diabetes patient-derived islet beta cell-specific T cell clones.
The researchers wanted to know if re-educating a patient's lymphocytes had the potential to address the autoimmunity concerns in a way that reduced donor risk, minimized ethical concerns, and avoided graft-versus-host disease.
C-peptide production at baseline in Group B was less than the minimum sensitivity of the test following a 75-g oral glucose tolerance. They had marked improvement at 12 weeks that continued to 40 weeks (P=0.026). The control group showed no changes at any time.
The median daily dose of insulin was reduced by 38% at 12 weeks (36 ± 13.2 units/day versus 22 ± 1.8 units/day) and 25% in the more severe group (48 ± 7.4 units/day versus 36 ± 4.4 units/day). These were maintained through the entire 24 weeks this measure was tracked.
Median hemoglobin A1C showed similar results.
In Group A the median was lowered from 8.73% ± 2.49 at baseline to 6.82% ± 0.49 at 12 weeks after treatment (P=0.019). This measure fell 1.68% ± 0.42 at 12 weeks in Group B with no change in the controls (P=0.86). These indicated to the authors that immune education of cord blood stem cells could lead to regeneration of islet beta cell function.
They also measured changes in the CD4+CD25+Foxp3+ regulatory T lymphocytes (Tregs) to see if measures of autoimmunity were altered. The percentage of Tregs in peripheral blood was significantly increased at 4 weeks in the treatment groups but not in the sham controls (P<0.0001).
There was no evidence of transfer of the cord blood stem cells to the patients as a result of the process of treating the lymphocytes, according to the investigators.
"This trial provides powerful evidence that exposing a patient's lymphocytes to [cord blood stem cells] can achieve the two essential outcomes required to cure T1D: reversal of autoimmunity and regeneration of islet beta cells," wrote the authors. "Importantly, the trial provides additional support for the mechanisms of [cord blood stem cells]-mediated immune response and demonstrates these mechanisms are apparent and lasting in patients."
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