title: 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.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov number, NCT01415726.
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 W, Polk Street, Chicago, IL 60612, USA. yzhaowhl@yahoo.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhaoshun
authors.initials: Z
authors.lastname: Jiang
authors.forename: Tingbao
authors.initials: T
authors.lastname: Zhao
authors.forename: Mingliang
authors.initials: M
authors.lastname: Ye
authors.forename: Chengjin
authors.initials: C
authors.lastname: Hu
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Yin
authors.forename: Yana
authors.initials: Y
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shanfeng
authors.initials: S
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Hatim
authors.initials: H
authors.lastname: Thaker
authors.forename: Summit
authors.initials: S
authors.lastname: Jain
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Li
authors.forename: Yalin
authors.initials: Y
authors.lastname: Diao
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Fisk
authors.forename: Heng
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D018920:Coculture Techniques; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000601:surgery*; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000637:transplantation*; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D056747:Immunomodulation / Q000187:drug effects / Q000276:immunology; D007333:Insulin Resistance / Q000276:immunology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D039902:Multipotent Stem Cells / Q000276:immunology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D007004:Hypoglycemic Agents