An immune regulator from healthy cord blood stem cells (CB-SCs) can “educate” the T cells of a person with type 1 diabetes (T1D), enabling the pancreas to produce insulin….
Yong Zhao, MD, PhD, from the University of Illinois at Chicago, and colleagues base their “stem cell educator therapy” on observations that multipotent stem cells from human cord blood can alter regulatory T cells (Tregs) and islet B cell–specific T-cell clones. The new approach alters autoimmunity both in non-obese diabetic mice and in islet B cells from patients with diabetes.
In a small, open-label trial, a single treatment reduced the median daily dose of required insulin by 38% at 12 weeks for patients with moderate T1D and some B-cell function (36 ± 13.2 U/day at baseline vs 22 ± 1.8 U/day 12 weeks post-treatment), and by 25% in patients with severe T1D and no residual function (48 ± 7.4 U/day at baseline vs 36 ± 4.4 U/day 12 weeks post-treatment). The investigators saw no change in insulin requirements among the control group.
The researchers circulated lymphocytes from patients’ blood in a closed-loop “stem cell educator,” co-culturing the cells for 2 to 3 hours with adherent CB-SCs from healthy donors. The device sandwiches CB-SCs between 9 discs of a hydrophobic material, with a top cover plate and a lower collecting plate through which the lymphocytes exit. The investigators infused the “educated” lymphocytes into the patients and measured both levels of C-peptide and glycated hemoglobin and indicators of immune function at 4, 12, 24, and 40 weeks.
Investigators conducted this open-label, phase 1/2 clinical trial at the General Hospital of Jinan Military Command in China from October 2010 until January 2011, 15 patients (median age, 29 years [range, 15 – 41 years]; median diabetic history, 8 years [range, 1 – 21 years]) received a single treatment. Three control patients received a sham treatment lacking cells.
Primary endpoints were feasibility (change in C-peptide secretion), safety by 12 weeks, and preliminary evidence of improved B cell function by 24 weeks. Immune modulation was a secondary end point.
Overall, the treated individuals displayed better C-peptide and glycated hemoglobin A1c values, lower daily requirement for insulin, and decreased autoimmunity.
Patients with moderate T1D had improved fasting C-peptide levels at 12 and 24 weeks. Those with severe T1D showed successive improvement in fasting C-peptide levels.
A1c levels for patients with moderate T1D fell from 8.73% ± 2.49% at baseline to 7.67% ± 1.03% at 4 weeks (P = .036), and to 6.82% ± 0.49% at 12 weeks post-treatment. For those with severe T1D, A1c levels fell 1.68% ± 0.42% at 12 weeks post-treatment, with no change seen in the control group.
Stem cell education significantly increased the percentage of Tregs in peripheral blood, as well as levels of CD28 and inducible co-stimulator. Cytokine balance improved. The CB-SCs produce an autoimmune regulator which may eliminate autoreactive T cells.
“This innovative approach may provide CB-SC-mediated immune modulation therapy for multiple autoimmune diseases while mitigating the safety and ethical concerns associated with other approaches,” conclude the researchers.
BMC Med. Published online January 10, 2012.