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Reversal of type 1 diabetes via islet beta cell regeneration following immunemodulation by cord blood-derived multipotent stem cells.BMC Medicine 2012, 10:3
ArticleYong Zhao1*, Zhaoshun Jiang2, Tingbao Zhao3, Mingliang Ye4, Chengjin Hu5,
Zhaohui Yin2, Heng Li6, Ye Zhang7, Yalin Diao4, Yunxiang Li4, Yingjian Chen5,
Xiaoming Sun5, Mary Beth Fisk8, Randal Skidgel9, Mark Holterman10, Bellur
Prabhakar11, Theodore Mazzone1
Abstract
Background
Inability to control autoimmunity is the primary barrier to developing a cure for
type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem
cells (CB-SCs) can control autoimmune responses by altering regulatory T cells
(Tregs) and human islet ? cell-specific T cell clones offers promise for a new
approach to overcome the autoimmunity underlying T1D.
Methods
We developed a procedure for Stem Cell Educator therapy in which a patient?s
blood is circulated through a closed-loop system that separates lymphocytes
from the whole blood and briefly co-cultures them with adherent CB-SCs before
returning them to the patient?s circulation. In an open-label, phase1/phase 2
study, patients (n = 15) with T1D received one treatment with the Stem Cell
Educator. Median age was 29 years (range: 15 to 41), and median diabetic
history was 8 years (range: 1 to 21).
Results
Stem Cell Educator therapy was well tolerated in all participants with minimal
pain from two venipunctures and no adverse events. Stem Cell Educator therapy
can markedly improve C-peptide levels, reduce the median glycated hemoglobin
A1C (HbA1C) values, and decrease the median daily dose of insulin in patients
with some residual ? cell function (n = 6) and patients with no residual pancreatic
islet ? cell function (n = 6). Treatment also produced an increase in basal and
glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up.
Individuals who received Stem Cell Educator therapy exhibited increased
expression of co-stimulating molecules (specifically, CD28 and ICOS), increases
in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3
cytokine balance.
Conclusions
Stem Cell Educator therapy is safe, and in individuals with moderate or severe
T1D, a single treatment produces lasting improvement in metabolic control. Initial
results indicate Stem Cell Educator therapy reverses autoimmunity and promotes
regeneration of islet ? cells. Successful immune modulation by CB-SCs and the
resulting clinical improvement in patient status may have important implications
for other autoimmune and inflammation-related diseases without the safety and
ethical concerns associated with conventional stem cell-based approaches.
Trial registration: ClinicalTrials.gov number, NCT01350219
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