Hydrogels for delivery of muscle stem cells to diaphragm
用于将肌肉干细胞递送至隔膜的水凝胶
基本信息
- 批准号:10281444
- 负责人:
- 金额:$ 2.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-11-01 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAdhesionsAdhesivesAffectApoptosisBiocompatible MaterialsBiological AssayBone RegenerationBypassC57BL/6 MouseCaringCell SurvivalCell TransplantationCell physiologyCellsCessation of lifeCollagenDefectDifferentiation AntigensDimensionsDuchenne muscular dystrophyDystroglycanDystrophinElectrodesEncapsulatedEngineeringEngraftmentEuthanasiaExtracellular MatrixFiberFormulationFrequenciesGelGene ExpressionGenetic DiseasesGoalsHarvestHeart failureHistologicHydrogelsImageImmunofluorescence ImmunologicIn Situ Nick-End LabelingIn VitroInferiorInjectableInjectionsIntegrinsIsometric ExerciseLeadLife ExpectancyLigandsLimb structureLocationMaleimidesMeasuresMechanical ventilationMechanicsMethodsMusMuscleMuscle WeaknessMuscle satellite cellMuscular AtrophyMusculoskeletalNatural regenerationNeuromuscular JunctionNewborn InfantOutcomeOutputPatientsPeptide HydrolasesPeptidesPlatinumProteinsQuality of lifeRadialRegenerative responseRespiratory DiaphragmRespiratory FailureRespiratory physiologyReverse Transcriptase Polymerase Chain ReactionRoleSarcolemmaStainsStructureSurfaceTestingThinnessTissuesTransducersTransplantationVertebral columnWorkX-Linked Genetic Diseasesagedbasebioimagingcell behaviorcrosslinkdensitydesigndisabilityimprovedimproved functioningin vivo imaging systemmalepalliativeparent grantprematurereceptor bindingrespiratoryresponserestorationsatellite cellstem cell deliverysyndecansynthetic peptidetargeted deliverytissue fixingventilation
项目摘要
PROJECT ABSTRACT
Duchenne muscular dystrophy (DMD) is an X-linked genetic disease that affects ~1 in 3,500 newborn males and
is characterized by progressive muscle wasting and weakness. As a result, patients suffer from ambulatory
disability, cardiac failure, and respiratory failure, the latter of which is a major contributor to premature death.
Current treatments for respiratory care remain palliative, as there is no cure for DMD. The primary cause for
DMD is the absence of functional dystrophin, a protein that provides structural support between the sarcolemma
and extracellular matrix. A strategy for restoring dystrophin is to transplant satellite cells to a target muscle.
Although this strategy would not be an efficient method to treat DMD throughout the body, the diaphragm muscle
presents a viable and important target for the delivery of satellite cells due to its vital role in respiratory function.
Upon successful engraftment of satellite cells to the diaphragm muscle, dystrophin, muscle excitability, and
respiratory function can be restored, extending a DMD patient’s life expectancy, and improving the quality of life
by potentially bypassing the need for mechanical ventilation. Delivery of satellite cells to the diaphragm muscle
poses a challenge due to sub-optimal engraftment, survival, and function of transplanted cells, as well as the
diaphragm’s thin dimensions and deep-seated location. This project seeks to overcome these hurdles by
engineering a synthetic hydrogel-based bioactive cell injectable vehicle to deliver satellite cells to the dystrophic
diaphragm and promote survival, expansion, differentiation, and engraftment of transplanted cells to improve
diaphragm function. The goals of this proposal will be accomplished in a stepwise fashion. First, we will engineer
synthetic hydrogels functionalized with adhesive peptides to maintain and direct muscle satellite cell function in
3D, including adhesion, survival, expansion, and differentiation. Second, we will evaluate the extent to which
engineered hydrogels allow for delivery and engraftment of GFP+ muscle satellite cells in the diaphragm of
mdx/mTR mice and the extent to which the diaphragm’s function improves. Successful outcomes in this work
will have broad significance and impact by demonstrating the potential of this strategy as a treatment for
respiratory failure in DMD patients. Rather than relying on mechanically assisted ventilation, a patient receiving
this treatment can benefit from an extended and improved quality of life. Additionally, this work will build on a
broader goal to demonstrate that designing biomaterials for stem cell delivery and engraftment to
musculoskeletal tissue is a feasible strategy for encouraging regeneration of the targeted tissue.
项目摘要
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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Andres J Garcia其他文献
Andres J Garcia的其他文献
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{{ truncateString('Andres J Garcia', 18)}}的其他基金
Hydrogels for human beta cell survival, function and evasion of immune rejection
用于人类β细胞存活、功能和逃避免疫排斥的水凝胶
- 批准号:
10512947 - 财政年份:2022
- 资助金额:
$ 2.7万 - 项目类别:
Hydrogels for human beta cell survival, function and evasion of immune rejection
用于人类β细胞存活、功能和逃避免疫排斥的水凝胶
- 批准号:
10705265 - 财政年份:2022
- 资助金额:
$ 2.7万 - 项目类别:
Hydrogels for human beta cell survival, function and evasion of immune rejection
用于人类β细胞存活、功能和逃避免疫排斥的水凝胶
- 批准号:
10865870 - 财政年份:2022
- 资助金额:
$ 2.7万 - 项目类别:
BIOMATERIALS FOR STEM CELL DERIVED BETA CELL TRANSPLANTATION
用于干细胞衍生的 β 细胞移植的生物材料
- 批准号:
10517827 - 财政年份:2021
- 资助金额:
$ 2.7万 - 项目类别:
BIOMATERIALS FOR STEM CELL-DERIVED BETA CELL TRANSPLANTATION
用于干细胞衍生的 β 细胞移植的生物材料
- 批准号:
10684716 - 财政年份:2021
- 资助金额:
$ 2.7万 - 项目类别:
BIOMATERIALS FOR STEM CELL-DERIVED BETA CELL TRANSPLANTATION
用于干细胞衍生的 β 细胞移植的生物材料
- 批准号:
10306891 - 财政年份:2021
- 资助金额:
$ 2.7万 - 项目类别:
BIOMATERIALS FOR STEM CELL-DERIVED BETA CELL TRANSPLANTATION
用于干细胞衍生的 β 细胞移植的生物材料
- 批准号:
10557968 - 财政年份:2021
- 资助金额:
$ 2.7万 - 项目类别:
BIOMATERIALS FOR STEM CELL-DERIVED BETA CELL TRANSPLANTATION
用于干细胞衍生的 β 细胞移植的生物材料
- 批准号:
10905940 - 财政年份:2021
- 资助金额:
$ 2.7万 - 项目类别:
Targeted delivery of immunomodulatory biologics for induction of immune privilege to allogeneic pancreatic islet grafts
靶向递送免疫调节生物制剂以诱导同种异体胰岛移植物的免疫特权
- 批准号:
10227259 - 财政年份:2020
- 资助金额:
$ 2.7万 - 项目类别:
Targeted delivery of immunomodulatory biologics for induction of immune privilege to allogeneic pancreatic islet grafts
靶向递送免疫调节生物制剂以诱导同种异体胰岛移植物的免疫特权
- 批准号:
10163042 - 财政年份:2020
- 资助金额:
$ 2.7万 - 项目类别:
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