Synthesis and High-Throughput In Vivo Characterization of Alginate Encapsulation Materials for Long-Term Islet

用于长期胰岛的海藻酸盐封装材料的合成和高通量体内表征

基本信息

  • 批准号:
    9982065
  • 负责人:
  • 金额:
    $ 77.51万
  • 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:
    2018-09-30 至 2022-05-31
  • 项目状态:
    已结题

项目摘要

Diabetes remains a global epidemic afflicting more than 300 million people worldwide, with incidence only expected to rise. Despite decades of research the current standard of care for those suffering from type I diabetes (TID) remains a rigorous regimen of blood glucose monitoring together with daily administrations of exogenous insulin and diabetic diet, these individuals still are challenged with untoward side effects due to complications of the disease in part the result of daily compliance issues. Islet transplantation has tremendous potential, but serious technological limitations remain. The lack of suitable biomaterials used for cell encapsulation is one of the key obstacles to clinical application. Cell encapsulation materials used to date are immunogenic, and lead to tissue capsule formation and cell graft failure. To address this challenge, here we propose the synthesis of 7000 candidate immune modulatory alginate- based hydrogel capsule formulations for cell encapsulation and a high-throughput in vivo method for identification of novel materials which can enable long-term protection and viability of transplanted donor pancreatic islet cells. A first-generation screen of 774 alginate formulations guides our design of this proposed second generation 7000 analogue structures. To enable increased throughput of screening, we propose to implant mixtures of different materials in the same implantation site. To pair the material identity with the observed material function, we are developing a next-generation sequencing (NGS) assay to determine material identity via a single nucleotide polymorphism (SNP) genotype of co-encapsulated HuVEC cells. Preliminary results using a 84-plex SNP NGS panel on 23 volunteers indicate high confidence genomic identification using limited NGS reads. Thus, a typical implantation of 200 alginate beads (1.5mm diameter) allows the simultaneous evaluation of 20 different implanted materials, with still sufficient independent beads per material to allow statistical analysis. In the course of this research project, the PI will first synthesize the new analogue library compounds. Subsequently, the PI will screen these materials in vivo using a xenogeneic transplantation of islets/HuVEC mixtures into a profibrotic C57BL/6 model rodents, that enables us to simultaneously screen up to 20-fold more distinct materials formulations in a single rodent. Next, the PI will examine the ability of leads (5-10) formulations to protect transplanted islet and restore normoglycemia in a T1D rodent model for up to 100 days. Finally lead formulations will be further vetted in healthy non-human primate studies. We anticipate that upon completion of this project, lead alginate materials for encapsulating islet cells will be identified that succeed in two different animal models (C57BL/6 mouse and macaque monkeys) and will be ready for pre-clinical tests under GLP/GMP conditions in preparation for an FDA IND submission.
糖尿病仍然是一种全球性流行病,全世界有3亿多人受其影响,仅发病率而已

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Omid Veiseh其他文献

Omid Veiseh的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Omid Veiseh', 18)}}的其他基金

Supplement to :Synthesis and High-Throughput In Vivo Characterization of Alginate Encapsulation Materials for Long-Term Islet….
补充:用于长期胰岛的藻酸盐封装材料的合成和高通量体内表征…。
  • 批准号:
    9925030
  • 财政年份:
    2018
  • 资助金额:
    $ 77.51万
  • 项目类别:
Synthesis and High-Throughput In Vivo Characterization of Alginate Encapsulation Materials for Long-Term Islet
用于长期胰岛的海藻酸盐封装材料的合成和高通量体内表征
  • 批准号:
    10161776
  • 财政年份:
    2018
  • 资助金额:
    $ 77.51万
  • 项目类别:
Synthesis and High-Throughput In Vivo Characterization of Alginate Encapsulation Materials for Long-Term Islet
用于长期胰岛的海藻酸盐封装材料的合成和高通量体内表征
  • 批准号:
    10417320
  • 财政年份:
    2018
  • 资助金额:
    $ 77.51万
  • 项目类别:
Enrichment of DNA/RNA Sequences based on Pre-equilibrium Hybridization Kinetics
基于预平衡杂交动力学的 DNA/RNA 序列富集
  • 批准号:
    10112940
  • 财政年份:
    2016
  • 资助金额:
    $ 77.51万
  • 项目类别:

相似海外基金

Étude des interactions de sorption et de séquestration de polluants sur des alginates
海藻酸盐污染物吸附与封存相互作用研究
  • 批准号:
    571945-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 77.51万
  • 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:
    $ 77.51万
  • 项目类别:
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:
    10402773
  • 财政年份:
    2018
  • 资助金额:
    $ 77.51万
  • 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:
    $ 77.51万
  • 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:
    $ 77.51万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了