Engineering an Islet Thread from zwitterionically modified alginates for type 1 diabetes
利用两性离子改性藻酸盐设计胰岛丝,用于治疗 1 型糖尿病
基本信息
- 批准号:10402773
- 负责人:
- 金额:$ 38.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAlginatesAreaBeta CellC57BL/6 MouseCanis familiarisCell SurvivalCell TransplantationCell physiologyCellsChemistryClinicalDevelopmentDevicesDiabetic mouseDiffusionDonor personEncapsulatedEngineeringEventFailureFamily suidaeFiberFibrosisForcepGlucoseGoalsHumanHydrogelsImmuneImmune systemImmunocompetentInfusion proceduresInjectionsInsulinInsulin-Dependent Diabetes MellitusIslet CellIslets of Langerhans TransplantationLaparoscopic Surgical ProceduresMechanicsMetabolicMicrocapsules drug delivery systemMusNanoporousNeonatalNutrientOutcomeOxygenPainPatientsPersonsPolymersProceduresPropertyRattusReportingReproducibilityResearchRetrievalRiskSCID Beige MouseSafetyScientistSourceStreptozocinStructureSupport SystemSurfaceSurgeonSurgical suturesSystemTestingTherapeutic EffectThinnessTimeTransplantationVertebral columnWorkbasebiomaterial compatibilitycanine modelcell replacement therapyclinical applicationclinically relevantclinically translatabledesigndiabeticexperienceexperimental studyhuman embryonic stem cellhuman stem cellsimplantationinnovationinterestisletislet stem cellsmedical complicationminimally invasivemouse modelnovelscale upstemstem cellstranslational potentialtransplant modelwasting
项目摘要
The objective of this project is to develop an advanced, clinically applicable islet/stem cell
encapsulation system for type 1 diabetes (T1D). Cell encapsulation and transplantation holds
enormous potential to treat T1D. Islets of allo or xeno origin or stem cell-derived beta cells are
encapsulated in a material or device that protects the cells from host immune rejection while
allowing facile mass transfer to maintain their survival and function. Numerous research groups
worldwide have made important progress, but clinical application of cell encapsulation has
remained elusive, due in a large part to the lack of a translatable encapsulation system that
meets the following basic but critical clinical needs: (1) It must be easy to handle, use and
transplant so that the encapsulation causes no harm to cells and the transplantation is minimally
invasive; (2) It must have sufficient biocompatibility (i.e. minimal or no formation of fibrosis),
robust mechanical stability and facile mass transfer (e.g. large surface area, short diffusion
distance and controllable permselectivity) so that the transplant can function for a long time, at
least several months; (3) It must be convenient to retrieve so that it can be removed or replaced
in the event of transplant failure or medical complications; (4) It must be scalable so that it can
deliver sufficient cell mass to produce a therapeutic effect. To meet these needs, we propose to
develop a novel, clinically translatable, TRAFFIC (Thread-Reinforced Alginate Fiber For Islet
enCapsulation) system from our newly developed, non-fibrotic zwitterionic-alginates for T1D
treatment. The critical innovations include both the structure design (i.e. incorporation a thin but
tough polymer thread into the center of a hydrogel fiber along its axis) and the hydrogel
chemistry (i.e. zwitterionically modified alginates). The inner polymer thread imparts mechanical
robustness and enables easy handling, implantation and retrieval, while the outer zwitterionic-
alginate hydrogel fiber provides necessary biocompatibility and facile mass transfer. We aim to
achieve long-term (>6 months) cures of diabetic mice using both rat islets and stem cell-derived
beta cells by optimizing the biocompatibility and mass transfer properties of the device. We will
also scale up the device and demonstrate its retrievability and functionality in dogs. The
anticipated outcome of this proposed research will be the development of a new cell
encapsulation system that is translatable for T1D patients.
本项目的目标是开发一种先进的、临床上可应用的胰岛/干细胞
1型糖尿病(T1 D)的治疗。细胞包封和移植保持
治疗T1 D的巨大潜力。同种或异种来源的胰岛或干细胞衍生的β细胞是
包封在保护细胞免受宿主免疫排斥的材料或装置中,
允许容易的质量转移以维持它们的存活和功能。众多研究小组
在世界范围内取得了重要进展,但细胞包封的临床应用
仍然难以捉摸,很大程度上是由于缺乏可翻译的封装系统,
满足以下基本但关键的临床需求:(1)必须易于操作、使用和
移植,使得包封不会对细胞造成伤害,并且移植是最低限度的,
侵入性;(2)它必须具有足够的生物相容性(即最小或无纤维化形成),
坚固的机械稳定性和容易的质量传递(例如,大表面积、短扩散
距离和可控的选择性渗透),使得移植物可以长时间地起作用,
至少几个月;(3)必须便于取回,以便拆除或更换
在移植失败或医疗并发症的情况下;(4)它必须是可扩展的,以便它可以
递送足够的细胞质量以产生治疗效果。为了满足这些需求,我们建议
开发一种新型的、临床上可转化的TRAFFIC(用于胰岛的螺纹增强藻酸盐纤维
enCapsulation)系统,从我们新开发的非纤维化两性离子藻酸盐用于T1 D
治疗关键的创新包括结构设计(即结合薄但
沿着其轴进入水凝胶纤维中心的坚韧聚合物线)和水凝胶
化学(即两性离子修饰的藻酸盐)。内部聚合物螺纹赋予机械
坚固耐用,易于操作、植入和取出,而外部的两性离子-
藻酸盐水凝胶纤维提供必要的生物相容性和易于传质。我们的目标是
使用大鼠胰岛和干细胞来源的干细胞实现糖尿病小鼠的长期(>6个月)治愈
通过优化装置的生物相容性和质量传递特性,我们将
还可放大器械并证明其在犬中的可回收性和功能性。的
这项研究的预期成果将是开发一种新的细胞,
这是一种可为T1 D患者翻译的封装系统。
项目成果
期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression.
- DOI:10.1126/sciadv.abn0071
- 发表时间:2022-07-22
- 期刊:
- 影响因子:13.6
- 作者:
- 通讯作者:
A Safe, Fibrosis-Mitigating, and Scalable Encapsulation Device Supports Long-Term Function of Insulin-Producing Cells.
- DOI:10.1002/smll.202104899
- 发表时间:2022-03
- 期刊:
- 影响因子:0
- 作者:Liu W;Flanders JA;Wang LH;Liu Q;Bowers DT;Wang K;Chiu A;Wang X;Ernst AU;Shariati K;Caserto JS;Parker B;Gao D;Plesser MD;Grunnet LG;Rescan C;Pimentel Carletto R;Winkel L;Melero-Martin JM;Ma M
- 通讯作者:Ma M
Specialty Tough Hydrogels and Their Biomedical Applications.
- DOI:10.1002/adhm.201901396
- 发表时间:2020-01
- 期刊:
- 影响因子:10
- 作者:Fuchs S;Shariati K;Ma M
- 通讯作者:Ma M
A predictive computational platform for optimizing the design of bioartificial pancreas devices.
- DOI:10.1038/s41467-022-33760-5
- 发表时间:2022-10-13
- 期刊:
- 影响因子:16.6
- 作者:
- 通讯作者:
Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.
- DOI:10.1002/advs.202003708
- 发表时间:2021-09
- 期刊:
- 影响因子:0
- 作者:Wang X;Brown NK;Wang B;Shariati K;Wang K;Fuchs S;Melero-Martin JM;Ma M
- 通讯作者:Ma M
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{{ truncateString('Minglin Ma', 18)}}的其他基金
Engineering an Islet Thread from zwitterionically modified alginates for type 1 diabetes
利用两性离子改性藻酸盐设计胰岛丝,用于治疗 1 型糖尿病
- 批准号:
9910390 - 财政年份:2018
- 资助金额:
$ 38.91万 - 项目类别:
Vascular networks genetically engineered for protein drug delivery
用于蛋白质药物输送的基因工程血管网络
- 批准号:
10457445 - 财政年份:2015
- 资助金额:
$ 38.91万 - 项目类别:
Vascular networks genetically engineered for protein drug delivery
用于蛋白质药物输送的基因工程血管网络
- 批准号:
10297294 - 财政年份:2015
- 资助金额:
$ 38.91万 - 项目类别:
Vascular networks genetically engineered for protein drug delivery
用于蛋白质药物输送的基因工程血管网络
- 批准号:
10617773 - 财政年份:2015
- 资助金额:
$ 38.91万 - 项目类别:
Organogenesis in microcapsules: developing an efficient and scalable organoid culture platform
微胶囊中的器官发生:开发高效且可扩展的类器官培养平台
- 批准号:
8952452 - 财政年份:2015
- 资助金额:
$ 38.91万 - 项目类别:
相似海外基金
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- 批准号:
571945-2022 - 财政年份:2022
- 资助金额:
$ 38.91万 - 项目类别:
University Undergraduate Student Research Awards
Engineering an Islet Thread from zwitterionically modified alginates for type 1 diabetes
利用两性离子改性藻酸盐设计胰岛丝,用于治疗 1 型糖尿病
- 批准号:
9910390 - 财政年份:2018
- 资助金额:
$ 38.91万 - 项目类别:
ALGIPRO - Alginates by Production Scale Fermentation and Epimerisation
ALGIPRO - 通过生产规模发酵和差向异构化生产海藻酸盐
- 批准号:
102148 - 财政年份:2016
- 资助金额:
$ 38.91万 - 项目类别:
Collaborative R&D
Bioactive Alginates and Obesity
生物活性藻酸盐与肥胖
- 批准号:
BB/G00563X/1 - 财政年份:2008
- 资助金额:
$ 38.91万 - 项目类别:
Research Grant