Cellular Therapy for Type 1 Diabetes using Mesenchymal Stem Cells
使用间充质干细胞进行 1 型糖尿病的细胞疗法
基本信息
- 批准号:10599910
- 负责人:
- 金额:$ 62.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAftercareAgeAllogenicArea Under CurveAttenuatedAutoimmuneAutoimmune DiseasesAutoimmune ResponsesAutoimmunityAutologousBeta CellBiological MarkersBone MarrowC-PeptideCD80 geneCD86 geneCell CountCell DeathCell TherapyCell physiologyCellsClinical DataClinical TreatmentClinical TrialsDNADataDiabetes MellitusDiseaseDoseDouble-Blind MethodEnrollmentFatty acid glycerol estersFundingGoalsGrantHarvestHyperglycemiaImmuneImmune responseImmune systemImmunosuppressionImmunotherapyInbred NOD MiceInflammatoryInfrastructureInfusion proceduresInstitutionInsulin-Dependent Diabetes MellitusInterdisciplinary StudyInterleukin-2InterventionLupusMHC Class II GenesMeasuresMesenchymalMesenchymal Stem CellsMetabolicMorbidity - disease rateNatural regenerationNewly DiagnosedPancreasPancreatic InjuryPatient RecruitmentsPatientsPeripheral Blood Mononuclear CellPlacebo ControlPlacebosPlastic Surgical ProceduresProceduresProliferatingPropertyRandomizedRegulatory T-LymphocyteReperfusion InjuryReportingRunningSafetySerious Adverse EventSerumSignal TransductionSourceStructure of beta Cell of isletSwedenTestingTh2 CellsTherapeuticTissuesTransforming Growth Factor beta ReceptorsUmbilical cord structureUnited StatesWound healing therapyadult stem cellautoreactive B cellclinical centercytokineefficacy evaluationexperienceimmune system functionimmunoregulationimprovedinsulin dependent diabetes mellitus onsetinsulin secretionisletmRNA Expressionmouse modelparticipant enrollmentpatient retentionpre-clinicalpreconditioningpreservationreceptorregeneration potentialregenerativeresponsesafety and feasibilitystandard of carestem cell expansionstem cell migrationstem cell therapystem cells
项目摘要
:
Two major hurdles must be overcome to cure type 1 diabetes (T1D): (i) the autoimmune response and (ii) destruction of insulin-secreting islets/β cells. Immunotherapies, including improved immune regulation using ex vivo expanded regulatory T-cell (Tregs) or low-dose interleukin-2 (IL-2), may be able to suppress autoimmunity. However, immunomodulation is not expected to directly stimulate regeneration of β cells. On the other hand, mesenchymal stromal/stem cells (MSCs) possess both immunomodulatory and regenerative properties and represent a promising new intervention for autoimmune diseases. MSCs are an accepted therapeutic for wound healing in plastic surgery applications and are being tested in clinical trials for the treatment of autoimmune and inflammatory diseases, ischemia reperfusion injuries, diabetes and other diseases. Our group and others found that after infusion into spontaneous non-obese diabetic (NOD) mice, MSCs migrated into the injured pancreas, reduced hyperglycemia and attenuated Th1 immune responses concomitant with the expansion/proliferation of Tregs. Most importantly, MSC infusion led to increased mRNA expression of IL-2 and TGF-β receptors in pancreatic Treg cells in NOD mice. A pilot clinical trial in Sweden showed that a single infusion of autologous bone marrow-derived MSCs preserved insulin secretion in adult patients with new-onset T1D. This study has yet to be systemically tested in patients in the United States and no mechanistic studies have been reported that explain the benefit observed. MSCs derived from umbilical cord (UC-MSCs) show greater cell yield, a less invasive harvesting procedure with associated reduced morbidity, and stronger immunosuppressive and regenerative potential and are a popular source for cell therapy. Based on the above principles and the successful patient enrollment in our one-year R01 grant, we propose a renewal of a randomized, double-blind, placebo- controlled, single-center clinical trial to determine the efficacy of UC-MSC therapy in patients with new-onset T1D. Our working hypothesis is that systemic administration of MSCs freshly expanded ex vivo reduces progression of diabetes and preserves insulin secretion through restoring normal function of the immune system and preservation/improvement of pancreatic β cells in patients with T1D. We will test this hypothesis by the following aims: (i). Determine the safety and efficacy of MSC therapy in patients with new-onset T1D when added to standard-of-care, and (ii) Define the mechanisms of protection and elucidate biomarker(s) of efficacy of MSC therapy in T1D patients. The early safety of MSC therapy is documented in our first 7 adult patients age 18-30 enrolled over 7 months and from multiple MSC Trials for various diseases. MSCs may constitute an important therapeutic advancement for T1D.
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项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Clathrin-mediated Endocytosis of Alpha-1 Antitrypsin is Essential for its Protective Function in Islet Cell Survival.
网格蛋白介导的 Alpha-1 抗胰蛋白酶内吞作用对于其在胰岛细胞存活中的保护功能至关重要。
- DOI:10.7150/thno.31647
- 发表时间:2019
- 期刊:
- 影响因子:12.4
- 作者:Wang,Jingjing;Gou,Wenyu;Kim,Do-Sung;Strange,Charlie;Wang,Hongjun
- 通讯作者:Wang,Hongjun
P.150: Alpha-1 Antitrypsin Engineered Mesenchymal Stromal Cells Improves Human Islet Survival via Regulation of Macrophage Activation.
P.150:Alpha-1 抗胰蛋白酶工程化的间充质基质细胞通过调节巨噬细胞激活来改善人类胰岛的存活。
- DOI:
- 发表时间:2021
- 期刊:
- 影响因子:6.2
- 作者:Wang,Hongjun
- 通讯作者:Wang,Hongjun
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Hongjun Wang其他文献
Hongjun Wang的其他文献
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{{ truncateString('Hongjun Wang', 18)}}的其他基金
Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Chronic Pancreatitis and Its Associated Pain
间充质干细胞治疗慢性胰腺炎及其相关疼痛的安全性和有效性
- 批准号:
10721284 - 财政年份:2023
- 资助金额:
$ 62.86万 - 项目类别:
Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT Patients
自体 BM-MSC 和胰岛联合移植可增强 TP-IAT 患者的胰岛存活和功能
- 批准号:
10474572 - 财政年份:2021
- 资助金额:
$ 62.86万 - 项目类别:
Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT Patients
自体 BM-MSC 和胰岛联合移植可增强 TP-IAT 患者的胰岛存活和功能
- 批准号:
10315988 - 财政年份:2021
- 资助金额:
$ 62.86万 - 项目类别:
Autologous BM-MSCs and Islet Co-transplantation to Enhance Islet Survival and Function in TP-IAT Patients
自体 BM-MSC 和胰岛联合移植可增强 TP-IAT 患者的胰岛存活和功能
- 批准号:
10640946 - 财政年份:2021
- 资助金额:
$ 62.86万 - 项目类别:
hAAT-engineered Mesenchymal Stem Cells for the Treatment of Chronic Pain
hAAT 工程改造的间充质干细胞用于治疗慢性疼痛
- 批准号:
10292900 - 财政年份:2019
- 资助金额:
$ 62.86万 - 项目类别:
hAAT-engineered Mesenchymal Stem Cells for the Treatment of Chronic Pain
hAAT 工程改造的间充质干细胞用于治疗慢性疼痛
- 批准号:
10044402 - 财政年份:2019
- 资助金额:
$ 62.86万 - 项目类别:
hAAT-engineered Mesenchymal Stem Cells for the Treatment of Chronic Pain
hAAT 工程改造的间充质干细胞用于治疗慢性疼痛
- 批准号:
10515305 - 财政年份:2019
- 资助金额:
$ 62.86万 - 项目类别:
Cellular Therapy for Type 1 Diabetes using Mesenchymal Stem Cells
使用间充质干细胞进行 1 型糖尿病的细胞疗法
- 批准号:
10376342 - 财政年份:2019
- 资助金额:
$ 62.86万 - 项目类别:
Micro- and nanofiber enabled biomimetic periosteum for bone repair and reconstruction
微米和纳米纤维仿生骨膜用于骨修复和重建
- 批准号:
9026932 - 财政年份:2016
- 资助金额:
$ 62.86万 - 项目类别:
Micro- and nanofiber enabled biomimetic periosteum for bone repair and reconstruction
微米和纳米纤维仿生骨膜用于骨修复和重建
- 批准号:
9755362 - 财政年份:2016
- 资助金额:
$ 62.86万 - 项目类别:
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