MSC Encapsulation with Thin Gel Coating

具有薄凝胶涂层的 MSC 封装

基本信息

  • 批准号:
    9383973
  • 负责人:
  • 金额:
    $ 68.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-15 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

Mesenchymal stem cell (MSC) therapies are currently in widespread clinical testing for a number of diseases, but a common theme of trials to date is the massive loss of the MSCs following transplantation. This outcome likely relates to the approach utilized for delivery – clinical trials typically utilize intravenous (iv) infusion of suspended cells. In contrast, encapsulation of cells in various materials has been widely explored in preclinical studies to enhance transplanted cell survival, but the resulting particles and devices have been too large to allow iv infusion, providing a significant practical obstacle to their clinical implementation. Further, as the bioactivity of MSCs is now widely ascribed to paracrine secretions, control over the secretome of the cells following transplantation may be crucial to their clinical success. We recently developed a highly efficient microfluidic process to encapsulate single cells in a very thin layer of hydrogel (~ 5 microns); this thin coating still allows cells to be infused intravenously, but dramatically increases both their survival and the duration of their secreted products in the bloodstream. We hypothesize this technology will provide a timely new tool for MSC therapies and dramatically expand their clinical utility. Here, we propose to further develop this new technology, and to study its utility in context of hematopoietic stem cell therapy (HSCT). We have put together a unique team to address the hypothesis underlying this project, with leaders in microfluidics technology (Weitz), biomaterials (Mooney), and hematopoietic stem cell (HSC) biology and HSCT (Scadden). We will pursue our objectives by: (1) Tune the chemical and physical properties of microgels, and scale-up the microfluidics technology to enable clinically relevant numbers of MSCs to be encapsulated with high efficiency, (2) Determine how MSC persistence and paracrine secretions following transplantation can be tuned, both qualitatively and quantitatively, by the chemical and physical properties of the encapsulating alginate hydrogel, and (3) Study the impact of gel-encapsulated MSCs, following intravenous infusion, on the treatment of graft versus host disease (GVHD) following HSCT in a rodent model. At the completion of these studies we will have validated the effectiveness and practicality of this approach to MSC therapy. Importantly, the results of these studies will help to define how the MSC secretome impacts the effectiveness of MSCs in GVHD, and the importance of immunoprotection of the MSCs following transplantation. Further, this approach is also likely to be broadly useful to the wide array of other clinical applications of MSCs and to the use of many other types of stem cells.
间充质干细胞(MSC)疗法目前在许多疾病的广泛临床试验中,

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)

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David J Mooney其他文献

Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells.
皮下可生物降解支架,用于重新刺激预施用的 CAR-T 细胞的抗肿瘤活性。
  • DOI:
    10.1038/s41551-024-01216-4
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    28.1
  • 作者:
    David K. Y. Zhang;Joshua M. Brockman;Kwasi Adu;Yutong Liu;Yoav Binenbaum;Irene de Lázaro;Miguel C. Sobral;Rea Tresa;David J Mooney
  • 通讯作者:
    David J Mooney
Angioid streaks in beta thalassaemia minor.
轻微β地中海贫血出现血管样条纹。
805-4 Biodegradable scaffolds incorporating vascular endothelial growth factor as a novel sustained delivery platform to induce angiogenesis
  • DOI:
    10.1016/s0735-1097(04)92001-3
  • 发表时间:
    2004-03-03
  • 期刊:
  • 影响因子:
  • 作者:
    Qinghua Sun;Ruth Chen;David J Mooney;Sanjay Rajagopalan;P.Michael Grossman
  • 通讯作者:
    P.Michael Grossman

David J Mooney的其他文献

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{{ truncateString('David J Mooney', 18)}}的其他基金

Viscoelasticity and T Cell Production
粘弹性和 T 细胞生产
  • 批准号:
    10566883
  • 财政年份:
    2022
  • 资助金额:
    $ 68.53万
  • 项目类别:
Engineering Skeletal Muscle WIth Biodegradable Hydrogels
用可生物降解水凝胶工程骨骼肌
  • 批准号:
    9894440
  • 财政年份:
    2019
  • 资助金额:
    $ 68.53万
  • 项目类别:
Scaffolds mimicking antigen presenting cells
模拟抗原呈递细胞的支架
  • 批准号:
    9789238
  • 财政年份:
    2018
  • 资助金额:
    $ 68.53万
  • 项目类别:
Scaffolds mimicking antigen presenting cells
模拟抗原呈递细胞的支架
  • 批准号:
    10001355
  • 财政年份:
    2018
  • 资助金额:
    $ 68.53万
  • 项目类别:
Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ
原位产生患者特异性抗原的生物材料癌症疫苗
  • 批准号:
    10053676
  • 财政年份:
    2017
  • 资助金额:
    $ 68.53万
  • 项目类别:
Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ
原位产生患者特异性抗原的生物材料癌症疫苗
  • 批准号:
    10305629
  • 财政年份:
    2017
  • 资助金额:
    $ 68.53万
  • 项目类别:
Biomaterial based breast cancer vaccine
基于生物材料的乳腺癌疫苗
  • 批准号:
    8830976
  • 财政年份:
    2013
  • 资助金额:
    $ 68.53万
  • 项目类别:
Biomaterial based breast cancer vaccine
基于生物材料的乳腺癌疫苗
  • 批准号:
    9047279
  • 财政年份:
    2013
  • 资助金额:
    $ 68.53万
  • 项目类别:
Building the Hematopoietic Stem Cell Niche
建立造血干细胞生态位
  • 批准号:
    8137505
  • 财政年份:
    2011
  • 资助金额:
    $ 68.53万
  • 项目类别:
Building the Hematopoietic Stem Cell Niche
建立造血干细胞生态位
  • 批准号:
    8704933
  • 财政年份:
    2011
  • 资助金额:
    $ 68.53万
  • 项目类别:

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海藻酸盐污染物吸附与封存相互作用研究
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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
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    $ 68.53万
  • 项目类别:
ALGIPRO - Alginates by Production Scale Fermentation and Epimerisation
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  • 批准号:
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Bioactive Alginates and Obesity
生物活性藻酸盐与肥胖
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