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Mesenchymal Stem Cells can Restore and Maintain Corneal Endothelial Function

Mesenchymal Stem Cells can Restore and Maintain Corneal Endothelial Function
间充质干细胞可以恢复和维持角膜内皮功能
批准号:
10465019
负责人:
Mohammad Mirazul Islam
金额:
$10.63万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-09-01 至 2024-08-31
关键词:
3-DimensionalAdipose tissueAdultAffectAgingAllogenicAnabolismAnimalsAqueous HumorAutologousAwardBiochemicalBiomechanicsBlindnessBlood CirculationBullaBullous KeratopathyCDKN2A geneCarpetCataract ExtractionCell Culture TechniquesCell CycleCell DensityCell Differentiation processCell SurvivalCell TherapyCell TransplantationCell physiologyCellsCellular biologyCicatrixClinicalClinical TrialsCoculture TechniquesComplementComplicationCorneaCorneal DiseasesCorneal EndotheliumCorneal StromaCulture MediaCyclin-Dependent Kinase InhibitorDataDehydrationDescemet&aposs membraneDevelopmentDiseaseDisease modelDislocationsEdemaEndothelial CellsEndotheliumEpithelialEpithelial CellsEvaluationExtracellular MatrixEyeEye diseasesFailureFuchs&apos Endothelial DystrophyFunctional disorderFundingFutureG1 PhaseGoalsGraft RejectionGrantHereditary DiseaseHomingHumanHydration statusIatrogenesisImmuneImmune responseIn SituIn VitroInflammatory ResponseInjuryKeratoplastyLeadLimbus CorneaeLiquid substanceMAP Kinase GeneMagnetic Resonance ImagingMagnetic nanoparticlesManuscriptsMentorsMesenchymal DifferentiationMesenchymal Stem CellsModelingMolecularMolecular BiologyMultipotent Stem CellsNatural regenerationNeuronsOperative Surgical ProceduresOrgan Culture TechniquesOryctolagus cuniculusPathway interactionsPatientsPhasePhenotypeProliferatingProteinsPumpResearchRiskRoleScientistSmall Interfering RNASourceStromal CellsStructure of sinus venosus of scleraSurfaceTechniquesTestingTherapeuticTimeTissue EngineeringTissue ModelTrainingTraining SupportTransforming Growth Factor betaTransplantationUndifferentiatedUnited States National Institutes of HealthVisual impairmentWritinganterior chamberbasebeta cateninbiomaterial compatibilitybone marrow mesenchymal stem cellcareercell injurycell typeclinical investigationcorneal epitheliumdensitydesignendothelial regenerationexperimental studyfaculty researchfeasibility testingfirst-in-humangene therapyin vivoin vivo Modelinhibitorleadership developmentlimbalmaterials sciencemechanotransductionmembermonolayermultidisciplinarynanoparticlenerve stem cellpost-transplantprofessorregeneration potentialscaffoldsiRNA deliveryskillsstem cell differentiationthree-dimensional modelingtumor

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Project Summary In this project, we propose to investigate the ability of mesenchymal stem cell (MSCs) to differentiate into functionally active corneal endothelial cells (CECs) to be transplanted in the diseased eye. As sources of MSCs, bone marrow MSCs (BM-MSCs), limbus MSCs (L-MSCs), and adipose derived MSCs (A-MSCs) will be evaluated. We will (1) determine the differentiation potential of different MSCs by varying numerous parameters and evaluate different molecular pathways involved in their differentiation, and (2) determine the ability of the differentiated cells to regenerate functionally active endothelium in diseased conditions. The differentiation, characterization, biocompatibility, and functionalization studies proposed here through in vitro, ex vivo, and in vivo studies will offer qualitative and quantitative information of the degree of biointegration and regenerative potential of the differentiated cells in contact with the host´s corneal cells and extracellular matrix. We expect that CECs differentiated from MSCs can proliferate in vivo after transplantation, maintaining the optimal hydration of the corneal stroma. If autologous or allogeneic MSCs can be differentiated to CECs and transplanted to recover normal endothelial function in patients suffering from endothelial diseases, without causing any immune or inflammatory response and without using whole donor corneas (DCs), this could simplify the treatment of corneal endothelial diseases and increase availability of DCs for other types of keratoplasty. Thus, I believe, this proposed research plan has the potential to revolutionize the treatment of corneal diseases, not only those affecting the corneal endothelium but also those affecting other corneal layers. The research aims are supported by the training plan focused on the acquisition of relevant multidisciplinary expertise in the field of cell and molecular biology, physiopathology, tissue-engineering, gene therapy, and material science. To this end, a “Mentoring Team” which includes the lead mentor, Dr. James Chodosh (MEE/ SERI), along with co-mentors, Dr. Miguel Gonzalez (SERI/UOC) and Professor Shigeto Shimmura (Keidai), has been assembled. Moreover, three independent collaborators will support our team in (1) the design of the studies related to MSCs differentiation and characterization (Dr. Garzon), (2) understanding of molecular pathways involved in the differentiation (Dr. Sabater), and (3) the nanoparticle based MRI detectable therapeutic strategies design (Dr. Patra). This group of mentors and collaborators will guide me during the K99 phase to achieve my long term career goal of becoming an academic scientist, and leader in my field with a strong independent research background. I envision that this award will provide me with an excellent platform to transition to an independent research faculty member (this includes the transition into the R00 phase) and in the long term, to successfully compete for independent NIH funding (R01 grant). My training will additionally be complemented by specialization courses during the mentored phase in the development, improvement of presentation and writing skills (grants and manuscripts), manuscript review, mentoring, and development of leadership abilities and lab management skills.
期刊论文(4)
专著(0)
科研奖励(0)
会议论文
DOI: 10.3390/pharmaceutics15061658
发表时间: 2023-06-05
期刊: Pharmaceutics
影响因子: 5.4
作者: [Malhotra K, Buznyk O, Islam MM, Edin E, Basu S, Groleau M, Dégué DS, Fagerholm P, Fois A, Lesage S, Jangamreddy JR, Šimoliūnas E, Liszka A, Patra HK, Griffith M]
通讯作者: Griffith M
DOI: 10.1016/j.copbio.2023.102947
发表时间: 2023-05
期刊: Current opinion in biotechnology
影响因子: 7.7
作者: [Bapan Pramanik;M. M. Islam-M.;H. Patra]
通讯作者: Bapan Pramanik;M. M. Islam-M.;H. Patra
DOI: 10.3389/fbioe.2022.883977
发表时间: 2022
期刊: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
影响因子: 5.7
作者: [Simpson, Fiona C., Islam, Mohammed Mirazul, Buznyk, Oleksiy, Edin, Elle, Groleau, Marc, Kozak-Ljunggren, Monika, Magrelli, Federica M., AbuSamra, Dina B., Argueeso, Pablo, Chodosh, James, Liszka, Aneta, Fagerholm, Per, Griffith, May]
通讯作者: Griffith, May
DOI: 10.1097/ico.0000000000003197
发表时间: 2023-05-01
期刊: CORNEA
影响因子: 2.8
作者: [Andre, Camille, Islam, Mohammad Mirazul, Paschalis, Eleftherios, Bispo, Paulo J. M.]
通讯作者: Bispo, Paulo J. M.
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