MSC Encapsulation with Thin Gel Coating
MSC Encapsulation with Thin Gel Coating
批准号:
9383973
负责人:
David J Mooney
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
项目状态:
已结题
起止时间:
2017-09-15 至 2020-06-30
关键词:
AddressAlginatesBiocompatible MaterialsBlood CirculationCell SurvivalCell TherapyCell TransplantationCell TransplantsCell physiologyCellsCellular biologyChemicalsClinicalClinical TrialsDevicesDiseaseEffectivenessEncapsulatedGelGoalsHematopoietic Stem Cell TransplantationHematopoietic stem cellsHydrogelsInfusion proceduresInjectableIntra-Arterial InfusionsIntravenousIntravenous infusion proceduresLifeMesenchymal Stem CellsMicrofluidicsMyocardial InfarctionOutcomePatientsProcessPropertyProteinsRodent ModelSavingsStem cellsTechnologyThinnessTimeTransplantationTreatment EfficacyUnited States National Institutes of HealthWorkbasechemical propertyclinical applicationclinically relevantflexibilitygraft vs host diseaseimprovedin vivointraperitonealnew technologynovel strategiesparacrineparticlephysical propertypreclinical studyresearch clinical testingscale upstem cell biologysuccesstoolviscoelasticityweb site
中文摘要
间充质干细胞(MSC)疗法目前在许多疾病的广泛临床试验中,
英文摘要
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.
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专著(0)
科研奖励(0)
会议论文
Viscoelasticity and T Cell Production
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批准号:10566883
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项目类别:
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资助金额:$56.89万
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财政年份:2022
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负责人:David J Mooney
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依托单位:
Engineering Skeletal Muscle WIth Biodegradable Hydrogels
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批准号:9894440
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项目类别:
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资助金额:$2.97万
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财政年份:2019
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负责人:David J Mooney
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依托单位:
Scaffolds mimicking antigen presenting cells
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批准号:9789238
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项目类别:
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资助金额:$60.0万
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财政年份:2018
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负责人:David J Mooney
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依托单位:
Scaffolds mimicking antigen presenting cells
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批准号:10001355
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项目类别:
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资助金额:$60.0万
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财政年份:2018
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负责人:David J Mooney
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依托单位:
Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ
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批准号:10053676
-
项目类别:
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资助金额:$42.59万
-
财政年份:2017
-
负责人:David J Mooney
-
依托单位:
Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ
-
批准号:10305629
-
项目类别:
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资助金额:$41.73万
-
财政年份:2017
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负责人:David J Mooney
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依托单位:
Biomaterial based breast cancer vaccine
-
批准号:8830976
-
项目类别:
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资助金额:$36.99万
-
财政年份:2013
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负责人:David J Mooney
-
依托单位:
Biomaterial based breast cancer vaccine
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批准号:9047279
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项目类别:
-
资助金额:$37.74万
-
财政年份:2013
-
负责人:David J Mooney
-
依托单位:
Building the Hematopoietic Stem Cell Niche
-
批准号:8137505
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项目类别:
-
资助金额:$76.61万
-
财政年份:2011
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负责人:David J Mooney
-
依托单位:
Building the Hematopoietic Stem Cell Niche
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批准号:8704933
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项目类别:
-
资助金额:$77.99万
-
财政年份:2011
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负责人:David J Mooney
-
依托单位:
Building the Hematopoietic Stem Cell Niche
-
批准号:8328560
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项目类别:
-
资助金额:$75.52万
-
财政年份:2011
-
负责人:David J Mooney
-
依托单位:
Building the Hematopoietic Stem Cell Niche
-
批准号:8495116
-
项目类别:
-
资助金额:$76.87万
-
财政年份:2011
-
负责人:David J Mooney
-
依托单位:
Engineering Capillary Networks
-
批准号:8462651
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项目类别:
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资助金额:$54.46万
-
财政年份:2010
-
负责人:David J Mooney
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依托单位:
Polymeric Matrices with Defined Cell Adhesion
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批准号:8035602
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项目类别:
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资助金额:$5.44万
-
财政年份:2010
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负责人:David J Mooney
-
依托单位:
Engineering Capillary Networks
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批准号:8286822
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项目类别:
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资助金额:$61.18万
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财政年份:2010
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负责人:David J Mooney
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依托单位:
Engineering Capillary Networks
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批准号:7889786
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项目类别:
-
资助金额:$60.18万
-
财政年份:2010
-
负责人:David J Mooney
-
依托单位:
Engineering Capillary Networks
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批准号:8071976
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项目类别:
-
资助金额:$57.14万
-
财政年份:2010
-
负责人:David J Mooney
-
依托单位:
Engineering Skeletal Muscle with Biodegradable Hydrogels
-
批准号:7831241
-
项目类别:
-
资助金额:$30.05万
-
财政年份:2009
-
负责人:David J Mooney
-
依托单位:
2004 Signal Transduction by Eng. Extracel. Matrices
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批准号:6754267
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项目类别:
-
资助金额:$2.2万
-
财政年份:2004
-
负责人:David J Mooney
-
依托单位:
Engineering capillary networks
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批准号:6952302
-
项目类别:
-
资助金额:$48.15万
-
财政年份:2003
-
负责人:David J Mooney
-
依托单位:
海外基金