Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial

BMC Med. 2013 Jul 9:11:160. doi: 10.1186/1741-7015-11-160.

Abstract

Background: The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease.

Methods: In an open-label, phase 1/phase 2 study, patients (N=36) with long-standing T2D were divided into three groups (Group A, oral medications, n=18; Group B, oral medications+insulin injections, n=11; Group C having impaired β-cell function with oral medications+insulin injections, n=7). All patients received one treatment with the Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient's circulation.

Results: Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61%±1.12 at baseline to 7.25%±0.58 at 12 weeks (P=2.62E-06), and 7.33%±1.02 at one year post-treatment (P=0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production.

Conclusions: Clinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in metabolic control for individuals with moderate or severe T2D who receive a single treatment. In addition, this approach does not appear to have the safety and ethical concerns associated with conventional stem cell-based approaches.

Trial registration: ClinicalTrials.gov number, NCT01415726.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Coculture Techniques
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / surgery*
  • Female
  • Fetal Blood / immunology
  • Fetal Blood / transplantation*
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Immunomodulation* / drug effects
  • Immunomodulation* / immunology
  • Insulin Resistance* / immunology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Multipotent Stem Cells / immunology
  • Multipotent Stem Cells / transplantation*
  • Stem Cell Transplantation / methods*
  • Transplantation, Autologous

Substances

  • Hypoglycemic Agents

Associated data

  • ClinicalTrials.gov/NCT01415726