Nanocarrier-targeted mesenchymal stem cells to treat inflammatory bowel disease
Nanocarrier-targeted mesenchymal stem cells to treat inflammatory bowel disease
批准号:
9093326
负责人:
Maria Teresa Abreu
金额:
$23.03万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-04-01 至 2018-03-31
关键词:
AddressAdverse effectsAffectAllogenicAnimal ModelAnimalsAnti-Inflammatory AgentsAnti-inflammatoryAreaAzathioprineBindingBiochemicalBlood VesselsCD11a AntigenCellsChildChildhoodChronicClinicalClinical TrialsColonCrohn&aposs diseaseDataDevelopmentDinoprostoneDiseaseDoseDrug Delivery SystemsEpithelialFailureFrightFutureGastroenterologistGeneticGlycocalyxGrowthHealedHome environmentHomingHumanICAM1 geneImmunomodulatorsInflammationInflammation MediatorsInflammatoryInflammatory Bowel DiseasesInfusion proceduresInjection of therapeutic agentInjuryInstitutesIntervention StudiesIntestinesLeadLocationMalignant NeoplasmsMedicalMesenchymal Stem CellsMinorityModelingMolecularMusNanotechnologyNatural ImmunityNitric OxideOutcomeParentsPatientsPermeabilityPlacebo EffectPlant RootsProductionPropertyRecoverySmall IntestinesSodium Dextran SulfateStem cellsSurgeonSystemic TherapyTNF geneTestingTherapeutic AgentsTimeTissuesTransforming Growth Factor betaTranslatingUlcerUmbilical cord structureUniversitiesVeinsVenousWorkWound Healingbasecytokineearly onsethealingimprovedinfliximabintercellular cell adhesion moleculeinterestlarge bowel Crohn&aposs diseasemouse modelmultidisciplinarynanocarriernanoparticleoutcome forecastparticlepublic health relevancerepairedstatisticsstem cell therapysuccesstargeted deliverytraditional therapytumorigenic
中文摘要
英文摘要
DESCRIPTION (provided by applicant): Mesenchymal stem cells (MSCs) have been proposed as alternative beneficial therapies for inflammatory bowel disease (IBD), in particular in Crohn's disease (CD), because of their anti-inflammatory properties, such as secretion of TGFβ, PGE2, and nitric oxide. Moreover, they are thought to home to areas where there is tissue damage. CD is characterized often by deep ulcerations in the small intestine and in the colon and patients with deep colonic ulcerations have a worse prognosis. Although medical therapy is directed at trying to achieve mucosal healing, it is a minority of patients that achieve
complete mucosal healing. Therefore, there is a critical need for therapies that will improve these statistics. Ideally, patients want therapies directed at healing and that can be used intermittently when the disease recurs, rather than using a chronic treatment. MSCs have been tried in a variety of contexts in CD. They have been used in local injections in patients with perianal fistulizing disease, as well as in systemic therapy for CD. Patients received allogeneic MSCs in a clinical trial, but, unfortunately, there was an extremely high placebo response rate. Another study used umbilical cord vein stem cells, but the trial was stopped early because of venous complications from the stem cell infusion. In both cases, one of the issues remaining is determining whether the lack of effect is due to lack of specific targeting of these stem cells to the gut, which results in need for administration of high doses of cells in order for just few to ultimately home to the intestine. Another concern of MSC therapy relates to whether stem cells reach other tissues beyond the intestine, and since these are stem cells, they may become tumorigenic in a different location. To overcome the aforementioned potential negative effects of stem cells, we aim to test whether targeted delivery of MSCs to the gut will result in an effective
safe therapy for IBD. Specifically, we will investigate if nanoparticle-targeted MSCs will be more beneficial than non-targeted MSCs in the treatment of IBD in murine models. We hypothesize that by targeting MSCs to the gut vasculature we will decrease inflammation and shorten the time to recovery. We believe that mechanistically this will occur through increased availability of
these cells in the tissue of interest, as well as through local production of growth factors such a TGFβ by these cells. We have chosen to target MSCs employing the ICAM ligand as the targeting molecule because of the high expression of ICAM and its binding partners in the inflamed IBD intestine.
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会议论文
University of Miami IBD Genetic Research Center: Understanding the Genetic Architecture of IBD in the LatinX Community
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批准号:10543290
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项目类别:
-
资助金额:$53.6万
-
财政年份:2022
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负责人:Maria Teresa Abreu
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依托单位:
University of Miami IBD Genetic Research Center: Understanding the Genetic Architecture of IBD in the LatinX Community
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批准号:10707450
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项目类别:
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资助金额:$54.04万
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财政年份:2022
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负责人:Maria Teresa Abreu
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依托单位:
Translational Research Training in Gastroenterology and Hepatology
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批准号:9906212
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项目类别:
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资助金额:$9.88万
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财政年份:2018
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负责人:Maria Teresa Abreu
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依托单位:
Translational Research Training in Gastroenterology and Hepatology
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批准号:10396477
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项目类别:
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资助金额:$17.29万
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财政年份:2018
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负责人:Maria Teresa Abreu
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依托单位:
INNATE IMMUNE PATHWAYS AND THE MICROBIOME IN HISPANICS WITH INFLAMMATORY BOWEL DISEASE
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批准号:9106760
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项目类别:
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资助金额:$47.72万
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财政年份:2016
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in Colitis Associated Neoplasia
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批准号:8761283
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项目类别:
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资助金额:$33.39万
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财政年份:2014
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in Colitis Associated Neoplasia
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批准号:9102094
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项目类别:
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资助金额:$33.39万
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财政年份:2014
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 and the microbiome in colitis associated neoplasia
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批准号:10361471
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项目类别:
-
资助金额:$34.54万
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财政年份:2014
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负责人:Maria Teresa Abreu
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依托单位:
Role of innate immunity and the microbiome in colitis-associated dysplasia
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批准号:10659444
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项目类别:
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资助金额:$38.94万
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财政年份:2014
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 and the microbiome in colitis associated neoplasia
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批准号:9906898
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项目类别:
-
资助金额:$34.54万
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财政年份:2014
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负责人:Maria Teresa Abreu
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依托单位:
Investing in the Future to Promote Diversity in GI Training
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批准号:8725146
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项目类别:
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资助金额:$14.84万
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财政年份:2012
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负责人:Maria Teresa Abreu
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依托单位:
Investing in the Future to Promote Diversity in GI Training
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批准号:9116828
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项目类别:
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资助金额:$14.84万
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财政年份:2012
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负责人:Maria Teresa Abreu
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依托单位:
Investing in the Future to Promote Diversity in GI Training
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批准号:8402759
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项目类别:
-
资助金额:$14.84万
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财政年份:2012
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负责人:Maria Teresa Abreu
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依托单位:
Investing in the Future to Promote Diversity in GI Training
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批准号:8542838
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项目类别:
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资助金额:$14.33万
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财政年份:2012
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负责人:Maria Teresa Abreu
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依托单位:
Toll- Like Receptor-Complex in Intestinal Epithelial Cells
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批准号:7839095
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项目类别:
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资助金额:$38.25万
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财政年份:2009
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in colitis-associated neoplasia
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批准号:8386504
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项目类别:
-
资助金额:$28.95万
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财政年份:2008
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in colitis-associated neoplasia
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批准号:7585547
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项目类别:
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资助金额:$31.62万
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财政年份:2008
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in colitis-associated neoplasia
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批准号:7996029
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项目类别:
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资助金额:$30.8万
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财政年份:2008
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in colitis-associated neoplasia
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批准号:8196887
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项目类别:
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资助金额:$30.8万
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财政年份:2008
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负责人:Maria Teresa Abreu
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依托单位:
Role of TLR4 in Acute and Chronic Murine Colitis
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批准号:7072282
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项目类别:
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资助金额:$16.55万
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财政年份:2005
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负责人:Maria Teresa Abreu
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依托单位:
海外基金