Autologous Hematopoietic Stem Cell Transplantation Modulates Immunocompetent Cells and Improves β-Cell Function in Chinese Patients with New Onset of Type 1 Diabetes

Li, Lirong; Shen, Shanmei; Ouyang, Jian; Hu, Yun; Hu, Limin; Cui, Weijuan; Zhang, Ning; Zhuge, Yuzheng; Chen, Bing; Xu, Jingyan; Zhu, Dalong

doi:10.1210/jc.2011-2188

Cited by 72 publications

(54 citation statements)

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“…Therapeutic interventions aimed at preserving b-cell mass at the time of diabetes onset thus far have shown transient and limited efficacy (2), mostly consisting of a less decline in insulin secretion but to improvement. Promising results in the experimental and clinical settings support the use of stem cell transplantation (SCT) or bone marrow (BM)-derived hematopoietic stem cells (HSCs) for the treatment of autoimmune diabetes (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Cai

et al. 2015

Diabetes Care

142

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OBJECTIVETo determine the safety and effects on insulin secretion of umbilical cord (UC) mesenchymal stromal cells (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D). RESEARCH DESIGN AND METHODSBetween January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 3 10 6 /kg UC-MSC, 106.8 3 10 6 /kg aBM-MNC through supraselective pancreatic artery cannulation) or standard care (control). Patients were followed for 1 year at 3-month intervals. The primary end point was C-peptide area under the curve (AUC C-Pep ) during an oral glucose tolerance test at 1 year. Additional end points were safety and tolerability of the procedure, metabolic control, and quality of life. RESULTSThe treatment was well tolerated. At 1 year, metabolic measures improved in treated patients: AUC C-Pep increased 105.7% (6.6 6 6.1 to 13.6 6 8.1 pmol/mL/180 min, P = 0.00012) in 20 of 21 responders, whereas it decreased 7.7% in control subjects (8.4 6 6.8 to 7.7 6 4.5 pmol/mL/180 min, P = 0.013 vs. SCT); insulin area under the curve increased 49.3% (1,477.8 6 1,012.8 to 2,205.5 6 1,194.0 mmol/mL/180 min, P = 0.01), whereas it decreased 5.7% in control subjects (1,517.7 6 630.2 to 1,431.7 6 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA 1c decreased 12.6% (8.6 6 0.81% [70.0 6 7.1 mmol/mol] to 7.5 6 1.0% [58.0 6 8.6 mmol/mol], P < 0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 6 0.9% [72.0 6 7.5 mmol/mol] to 8.8 6 0.9% [73 6 7.5 mmol/mol], P < 0.01 vs. SCT). Fasting glycemia decreased 24.4% (200.0 6 51.1 to 151.2 6 22.1 mg/dL, P < 0.002) and 4.3% in control subjects (192.4 6 35.3 to 184.2 6 34.3 mg/dL, P < 0.042). Daily insulin requirements decreased 29.2% in only the treated group (0.9 6 0.2 to 0.6 6 0.2 IU/day/kg, P = 0.001), with no change found in control subjects (0.9 6 0.2 to 0.9 6 0.2 IU/day/kg, P < 0.01 vs. SCT). CONCLUSIONSTransplantation of UC-MSC and aBM-MNC was safe and associated with moderate improvement of metabolic measures in patients with established T1D.

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confidence: 99%

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Cai

et al. 2015

Diabetes Care

142

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“…Several clinical trials-designed based on the preclinical successful targeting of components of innate and adaptive immune responses-performed thus far have failed to cure T1D (3,8); only in the anti-CD3 monoclonal antibody (mAb) trial (using teplizumab in the Protégé Study) did 5% of individuals become insulin independent (9). In this daunting scenario, a trial conducted by Voltarelli et al (10) succeeded in exploiting hematopoietic stem cells (HSCs) to treat new-onset T1D and achieved encouraging results, paving the way for another three trials, which were initiated worldwide (11,12). The rationale for the use of HSCs in treating subjects with T1D is based upon the immunoregulatory properties of HSCs, which may help to rescue peripheral tolerance toward pancreatic b-cells by reshaping the immune response (13,14).…”

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confidence: 99%

Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in New-Onset Type 1 Diabetes: A Multicenter Analysis

et al. 2014

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Type 1 diabetes (T1D) is one of the major autoimmune diseases affecting children and young adults worldwide. To date, the different immunotherapies tested have achieved insulin independence in <5% of treated individuals. Recently, a novel hematopoietic stem cell (HSC)-based strategy has been tested in individuals with new-onset T1D. The aim of this study was to determine the effects of autologous nonmyeloablative HSC transplantation in 65 individuals with new-onset T1D who were enrolled in two Chinese centers and one Polish center, pooled, and followed up for 48 months. A total of 59% of individuals with T1D achieved insulin independence within the first 6 months after receiving conditioning immunosuppression therapy (with antithymocyte globulin and cyclophosphamide) and a single infusion of autologous HSCs, and 32% remained insulin independent at the last time point of their follow-up. All treated subjects showed a decrease in HbA 1c levels and an increase in C-peptide levels compared with pretreatment. Despite a complete immune system recovery (i.e., leukocyte count) after treatment, 52% of treated individuals experienced adverse effects. Our study suggests the following: 1) that remission of T1D is possible by combining HSC transplantation and immunosuppression; 2) that autologous nonmyeloablative HSC transplantation represents an effective treatment for selected individuals with T1D; and 3) that safer HSC-based therapeutic options are required.The incidence of type 1 diabetes (T1D) has been significantly increasing worldwide in the last decade, thus becoming the most common autoimmune disorder in children (1). T1D is characterized by a selective and aggressive destruction of insulin-producing b-cells orchestrated by autoreactive T cells (2,3). Unfortunately, exogenous insulin therapy does not always achieve the necessary metabolic control (4), nor does it prevent the occurrence of disease-associated degenerative macrovascular and microvascular complications (5) or halt b-cell decline (6).The concept of the use of immunotherapeutic strategy to cure T1D has emerged from hallmark data generated using the NOD mouse model and has allowed for a better understanding of the pathogenesis of T1D (7). Several clinical trials-designed based on the preclinical successful targeting of components of innate and adaptive immune responses-performed thus far have failed to cure

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“…HCT has been promoted in polymyositis/dermatomyositis, Sjogren's syndrome, psoriatic arthritis and ankylosing arthritis, chronic inflammatory demyelinating polyneuropathy and autoimmune cytopenias, including hemolytic anemia, ITP, Evans syndrome and other rare combinations [115,116]. Promising preliminary results were registered in small groups of patients with type 1 diabetes (T1D) from Brazil [117,118], China [119,120], and Poland [121]. Preliminary lessons from these small trials suggest that: (i) majority of patients can reach independence of exogenous insulin for a period of few months to years; (ii) according to our knowledge, there were no described transplant-related deaths; and (iii) diabetic ketoacidosis at onset, probably due to a severe depletion of islet cells, can be a poor predicting factor.…”

Section: Hct In Other Autoimmune Diseasesmentioning

confidence: 99%

Hematopoietic Cell Transplantation for Autoimmune Diseases: A Review of History, Current State, and Future Issues

Resnick¹,

Metodiev²,

Lazarova³

2017

Immunotherapy - Myths, Reality, Ideas, Future

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Autoimmune diseases are characterized by recurrent attacks and remissions, but as a rule they progress and eventually cause a severe disability and death. The present chapter contains general characteristics of autoimmune disease pathogenesis, ways to cause immune tolerance by hematopoietic cell transplantation (HCT), clinical aspects of the treatment for established autoimmune diseases with a special attention to multiple sclerosis (MS) and systemic sclerosis (SSc). A profound analysis of authors' point of view and of the available literature has been performed. The promising results allows to consider HCT as a relevant treatment option for a certain autoimmune diseases.

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Autologous Hematopoietic Stem Cell Transplantation Modulates Immunocompetent Cells and Improves β-Cell Function in Chinese Patients with New Onset of Type 1 Diabetes

Abstract: AHSCT modulated lymphocytes and preserved β-cell function in Chinese patients with new onset of type 1 diabetes and diabetic ketoacidosis.

Cited by 72 publications

References 9 publications

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in New-Onset Type 1 Diabetes: A Multicenter Analysis

Hematopoietic Cell Transplantation for Autoimmune Diseases: A Review of History, Current State, and Future Issues

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