Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy
Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy
批准号:
8067052
负责人:
William L Lowe
金额:
$34.89万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-05-01 至 2014-04-30
关键词:
AddressAffectAngiogenic FactorApoptosisArchitectureAutoimmune ProcessBeta CellBloodBlood CirculationBrainCalcineurin inhibitorCell DeathCell SurvivalCell TherapyCell TransplantsCell physiologyCellsChronic DiseaseDevelopmentDiabetes MellitusEngraftmentEnvironmentExhibitsExposure toExtracellular MatrixFailureFatty acid glycerol estersFibroblast Growth Factor 2Glycolic-Lactic Acid PolyesterGrowth FactorHeartHepaticHormonesHyperglycemiaHypoxiaImmune systemImmunosuppressive AgentsInfiltrationInflammatoryInsulinInsulin-Dependent Diabetes MellitusInsulin-Like Growth Factor IIslet CellIslets of LangerhansIslets of Langerhans TransplantationLeftLiverMediatingMetabolicModelingMorphologyMusNutrientOrganPancreasPeptidesPeritonealPharmaceutical PreparationsPolymersPorosityProcessProlactinProteinsReactionReplacement TherapyRiskSecondary toSirolimusSourceStressSupporting CellTestingTimeTissuesToxic effectToxinTransplant RecipientsTransplantationVascular Endothelial Growth FactorsVascularizationWaste Productsangiogenesiscell growthconditioningexenatideimprovedin vivointerestisletliver transplantationmacrophagenovel strategiespreventpublic health relevancescaffoldsuccess
中文摘要
描述(由申请人提供):细胞疗法提供了一种治疗慢性疾病的新方法。通过分泌激素或其他因素来恢复受损器官的功能依赖于移植细胞的成功植入。移植细胞的移植需要细胞在移植后最初的缺氧环境中存活,与宿主血管系统连接以交换营养物质和废物,并将分泌因子输送到循环系统中。这样做需要创造一个促进移植细胞长期功能的环境。如果细胞供应有限,扩大体内移植移植物的方法也可能很重要。我们提出解决的假设是,微孔聚合物支架能够传递生物活性肽,可以创造一个微环境,促进细胞的植入,生存和增殖。细胞疗法的经典范例是用于治疗1型糖尿病的胰岛移植,其中胰腺中胰岛素分泌β细胞的破坏导致高血糖及其并发症。最近的试验证明了胰岛移植是有效的,但问题仍然存在。为了解决这些问题,我们建议将胰岛移植到能够释放影响宿主组织(例如,血管化)或增强移植胰岛功能的蛋白质的微孔支架上。这些因素将调节微环境,促进胰岛的移植、存活和功能。我们最近已经证明微孔支架可以作为胰岛移植的平台。具体目的如下:(i) 1)研究由孔隙度、孔径大小和稳定性定义的支架结构将影响胰岛植入和功能的假设。(ii)在小鼠糖尿病模型中,使用聚合物支架递送血管生成因子将改善胰岛移植后的存活和功能。(iii)验证聚合物支架提供抑制胰岛细胞死亡和/或增加移植后胰岛细胞质量的因子将增强胰岛植入和功能的假设。(iv)确定是否递送影响不同过程的生长因子组合(例如,血管生成和胰岛细胞存活和/或增殖)比递送单一因子更有效。这些研究有可能极大地推进胰岛移植的细胞治疗。
英文摘要
DESCRIPTION (provided by applicant): Cell-based therapies provide a novel approach to treating chronic diseases. Recapitulating a damaged organ's function by secreting hormones or other factors is dependent upon successful engraftment of transplanted cells. Engraftment of the transplanted cells requires that cells survive the initial hypoxic environment following transplantation, connect with the host vasculature for exchange of nutrients and waste products and also deliver secreted factors into the circulation. Doing this requires creating an environment that promotes long term function of the transplanted cells. If the cell supply is limited, approaches to expand the transplant graft in vivo may also be important. We propose to address the hypothesis that micro-porous polymer scaffolds capable of delivering biologically active peptides can create a microenvironment to promote cell engraftment, survival and proliferation. A classic paradigm for cell-based therapy is islet transplantation for treatment of type 1 diabetes in which destruction of insulin-secreting beta cells in the pancreas results in hyperglycemia and its complications. Recent trials have provided proof of concept that islet transplantation can be efficacious, yet problems remain. To address these problems, we are proposing to transplant islets on microporous scaffolds capable of releasing proteins that can influence the host tissue (e.g., vascularization) or enhance the functionality of the transplanted islets. These factors will condition the microenvironment to promote islet engraftment, survival, and function. We have recently shown that microporous scaffolds can serve as a platform for islet transplantation. The Specific Aims are as follows. (i) 1) To investigate the hypothesis that the scaffold architecture, as defined by porosity, pore size, and stability, will influence islet engraftment and function. (ii) To address the hypothesis that use of a polymer scaffold to deliver angiogenic factors will improve islet survival and function post-transplantation in a murine model of diabetes. (iii) To test the hypothesis that polymer scaffolds delivering factors that inhibit islet cell death and/or increase islet cell mass post-transplantation will enhance islet engraftment and function. (iv) To determine whether delivering a combination of growth factors that affect different processes (e.g., angiogenesis and islet cell survival and/or proliferation) is more efficacious than delivering a single factor. These studies have the potential to substantially advance cell therapies for islet transplantation.
PUBLIC HEALTH RELEVANCE: Transplantation of islets or, ultimately, insulin-secreting cells from other sources represents a potential cure for diabetes, which results from destruction of insulin-secreting cells by the immune system. To enhance cell replacement therapy for diabetes, we are developing scaffolds for transplantation of islets or insulin-secreting cells into peritoneal fat. These scaffolds provide a support for cell growth and can deliver proteins which will be to enhance cell survival and function following islet transplantation.
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会议论文
Glycemic Profiles and Pregnancy Outcomes Study (GLOSS)
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批准号:10227745
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项目类别:
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资助金额:$53.04万
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财政年份:2019
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负责人:William L Lowe
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依托单位:
Glycemic Profiles and Pregnancy Outcomes Study (GLOSS)
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批准号:10704001
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资助金额:$71.34万
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财政年份:2019
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负责人:William L Lowe
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Glycemic Profiles and Pregnancy Outcomes Study (GLOSS)
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批准号:10021649
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资助金额:$58.37万
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财政年份:2019
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负责人:William L Lowe
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依托单位:
Predicting Newborn and Childhood Adiposity: An Integrated Omics Approach
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批准号:10452488
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项目类别:
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资助金额:$57.71万
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财政年份:2018
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负责人:William L Lowe
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依托单位:
Predicting Newborn and Childhood Adiposity: An Integrated Omics Approach
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批准号:10188519
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项目类别:
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资助金额:$60.98万
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财政年份:2018
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负责人:William L Lowe
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依托单位:
Maternal Obesity and Gestational Diabetes: Impact on Metabolome
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批准号:8638966
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项目类别:
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资助金额:$43.18万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Genomics of Maternal Glycemia During Pregnancy
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批准号:8726979
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项目类别:
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资助金额:$15.1万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Maternal Obesity and Gestational Diabetes: Impact on Metabolome
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批准号:8503043
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项目类别:
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资助金额:$44.45万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Genomics of Maternal Glycemia During Pregnancy
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批准号:8582891
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项目类别:
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资助金额:$52.49万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Evolution of Fetal Human Fat Accretion During Development
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批准号:8581302
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项目类别:
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资助金额:$37.11万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Evolution of Fetal Human Fat Accretion During Development
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批准号:8856560
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项目类别:
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资助金额:$29.97万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Evolution of Fetal Human Fat Accretion During Development
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批准号:9047274
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项目类别:
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资助金额:$47.52万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Genomics of Maternal Glycemia During Pregnancy
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批准号:9285793
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项目类别:
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资助金额:$45.36万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Genomics of Maternal Glycemia During Pregnancy
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批准号:8857430
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项目类别:
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资助金额:$52.63万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Genetics and Evolution of Fetal Human Fat Accretion During Development
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批准号:8676792
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项目类别:
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资助金额:$34.34万
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财政年份:2013
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负责人:William L Lowe
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依托单位:
Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy
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批准号:8274742
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项目类别:
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资助金额:$34.94万
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财政年份:2010
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负责人:William L Lowe
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依托单位:
Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy
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批准号:7889716
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项目类别:
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资助金额:$32.96万
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财政年份:2010
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负责人:William L Lowe
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依托单位:
Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy
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批准号:8461627
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项目类别:
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资助金额:$32.5万
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财政年份:2010
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负责人:William L Lowe
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依托单位:
Replication of GWAS for Maternal Glycemia, Birthweight and their Interaction
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批准号:7743508
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项目类别:
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资助金额:$39.87万
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财政年份:2009
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负责人:William L Lowe
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依托单位:
GWA Mapping: Maternal Metabolism-Birth Weight Interactions
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批准号:7923473
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项目类别:
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资助金额:$6.5万
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财政年份:2009
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负责人:William L Lowe
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依托单位:
海外基金