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
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- 作者：Yong Zhao (1) (2)
Zhaoshun Jiang (3)
Tingbao Zhao (4)
Mingliang Ye (5)
Chengjin Hu (6)
Huimin Zhou (7)
Zhaohui Yin (3)
Yana Chen (8)
Ye Zhang (2)
Shanfeng Wang (2)
Jie Shen (2)
Hatim Thaker (1)
Summit Jain (1)
Yunxiang Li (2)
Yalin Diao (5)
Yingjian Chen (6)
Xiaoming Sun (6)
Mary Beth Fisk (9)
Heng Li (10) - 刊名：BMC Medicine
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：11
- 期：1
- 全文大小：400KB
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68. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/160/prepub - 作者单位：Yong Zhao (1) (2)
Zhaoshun Jiang (3)
Tingbao Zhao (4)
Mingliang Ye (5)
Chengjin Hu (6)
Huimin Zhou (7)
Zhaohui Yin (3)
Yana Chen (8)
Ye Zhang (2)
Shanfeng Wang (2)
Jie Shen (2)
Hatim Thaker (1)
Summit Jain (1)
Yunxiang Li (2)
Yalin Diao (5)
Yingjian Chen (6)
Xiaoming Sun (6)
Mary Beth Fisk (9)
Heng Li (10)
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
文摘
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