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
1 Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 W. Polk Street, Chicago, IL 60612, USA
2 Tianhe Stem Cell Biotechnologies Inc., 750 Shunhua Road, Jinan, Shandong 250055, PR China
3 Section of Endocrinology, General Hospital of Jinan Military Command, 25 Shifan Road, Jinan, Shandong 250031, PR China
4 Stem Cell Treatment Center, General Hospital of Jinan Military Command, 25 Shifan Road, Jinan, Shandong 250031, PR China
5 Section of Blood Transfusion, General Hospital of Jinan Military Command, 25 Shifan Road, Jinan, Shandong 250031, PR China
6 Section of Molecular Diagnostics, General Hospital of Jinan Military Command, 25 Shifan Road, Jinan, Shandong 250031, PR China
7 Section of Endocrinology, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang 050031, PR China
8 Department of Obstetrics, Jinan Central Hospital, Shandong University, 105 Jiefang Road, Jinan, Shandong 250031, PR China
9 Texas Cord Blood Bank, 6211 IH-10 west, San Antonio, TX 78201, USA
10 Department of Neurology, Jinan Central Hospital, Shandong University, 105 Jiefang Road, Jinan, Shandong 250031, PR China
BMC Medicine 2013, 11:160 doi:10.1186/1741-7015-11-160Published: 9 July 2013
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.
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.
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.
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.
ClinicalTrials.gov number, NCT01415726