Reversal of type 1 diabetes via islet ß cell regeneration following immune modulation by cord blood-derived multipotent stem cells.
BMC Med
; 10: 3, 2012 Jan 10.
Article
in En
| MEDLINE
| ID: mdl-22233865
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 ß 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 ß cell function (n=6) and patients with no residual pancreatic islet ß 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 ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Regeneration
/
Multipotent Stem Cells
/
Diabetes Mellitus, Type 1
/
Insulin-Secreting Cells
/
Immunomodulation
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspects:
Ethics
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
BMC Med
Journal subject:
MEDICINA
Year:
2012
Document type:
Article
Affiliation country:
United States