Myogenic stem cells in extraocular muscles
Myogenic stem cells in extraocular muscles
批准号:
8851073
负责人:
ZIPORA YABLONKA-REUVENI
金额:
$11.59万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-08-01 至 2016-07-31
关键词:
AddressAdultAgeAgingAnimal ModelAntigensAtrophicBasal laminaCell Culture TechniquesCell NucleusCell SeparationCellsCharacteristicsComplexDataDeteriorationDevelopmentDiseaseDuchenne muscular dystrophyDystrophinEndothelial CellsEndotheliumExhibitsEye MovementsGenesGlycoproteinsGoalsGrowthHarvestHeadHindlimbImpairmentKnockout MiceLifeLightLimb structureLinkLocationMaintenanceMesodermModelingMolecularMonitorMusMuscleMuscle FibersMuscle rehabilitationMuscle satellite cellMuscular AtrophyMuscular DystrophiesMyopathyPerformancePericytesPilot ProjectsPlayPopulationPreparationProcessProliferatingPropertyRegulatory ElementReporter GenesReportingReserve CellRespiratory DiaphragmRoleSkeletal MuscleSkeletal Muscle Satellite CellsSorting - Cell MovementSourceStem cellsSupporting CellTransgenic Organismsbasecell typefunctional statusin vivoinsightinterstitialmyogenesisnestin proteinorbit muscleprogenitorrehabilitation strategyrepairedsarcopeniasatellite cellskeletalstemtrait
中文摘要
项目摘要
眼外肌(extraocular muscle,EOM)是一组高度特化的控制眼球运动的骨骼肌
动作它们从头部中胚层发育而来,在分子上、解剖学上和
在生理上与其他骨骼肌不同。EOM具有独特的质量,
与肌营养不良蛋白-糖蛋白复合物损伤相关的肌营养不良。迪谢内
肌营养不良症和这种破坏性肌营养不良蛋白缺乏相关疾病的动物模型中,
眼外肌得以幸免,与对其他肌肉的严重早发性或迟发性损伤相反。具体特征
眼外肌中的肌源性祖细胞可能在这些肌肉的优先保留中起作用。令人惊奇的是,
对成人眼外肌中的肌源性干细胞和祖细胞知之甚少。的困难
分离用于收获原代细胞的EOM导致缺乏合适的细胞培养模型
目的在于鉴定支持眼外肌肌纤维终生维持的细胞的特性。
本申请提出破译三种细胞类型的细胞和分子特征
与肢体和膈肌相比,在眼外肌中显示出强劲的生长和更新特性,
这可能有助于保护眼外肌免受肌营养不良和年龄相关性萎缩的影响。
这些细胞类型是:a)卫星细胞,其被经典地认为是肌原性细胞的主要来源。
成体骨骼肌中的祖细胞; B)间质性肌源性祖细胞; c)微血管相关的
收缩细胞(即,周细胞),其可直接与肌纤维融合。建议的研究旨在:1)
表征肌细胞特异性标志物在卫星细胞和肌细胞小生境中的细胞表达,
眼外肌与肢体和膈肌; 2)比较肌源性干的生长和更新潜力
3)研究供体的潜力
来自EOM的卫星细胞和周细胞相对于肢体和膈肌有助于体内
肌肉修复来自携带各种报告基因的野生型和肌养蛋白缺失小鼠的细胞(用于追踪
不同的细胞类型和它们的后代)将在体内和培养物中进行研究。预期结果
的拟议研究将有助于更好地了解支持EOM的细胞环境
维持在成年生活中,并将提供新的见解,微血管相关的作用,
骨骼肌发生中的细胞。眼外肌肌源性祖细胞的进一步表征对于
开发治疗眼外肌疾病的修复策略。拟议的研究还将
关于衰老和肌营养不良蛋白缺乏肌肉中肌源性祖细胞功能状态的新认识,
为肌肉康复策略提供重要信息。
英文摘要
PROJECT SUMMARY
Extraocular muscles (EOMs) are a group of highly specialized skeletal muscles that control eye
movements. They develop from the head mesoderm and are molecularly, anatomically and
physiologically distinct from other skeletal muscles. EOMs possess a unique quality of being spared in
muscular dystrophies associated with impairments in the dystrophin-glycoprotein complex. In Duchenne
muscular dystrophy and in animal models of this devastating dystrophin deficiency-associated disease,
EOMs are spared, contrary to the severe early- or late-onset damage to other muscles. Specific traits of
myogenic progenitors in EOMs may play a role in the preferential sparing of these muscles. Surprisingly,
very little is known about the myogenic stem and progenitor cells in adult EOMs. The difficulty in
isolating EOMs for harvesting primary cells has resulted in the lack of appropriate cell culture models
aimed at identifying the properties of cells that support EOM myofiber maintenance through life.
This application proposes to decipher cellular and molecular characteristics of three cell types
that display robust growth and renewal properties in EOMs compared to limb and diaphragm muscles, a
distinction that may contribute to the sparing of EOMs from dystrophinopathy and age-linked atrophy.
These cell types are: a) satellite cells, which are classically recognized as the main source of myogenic
progenitors in adult skeletal muscle; b) interstitial myogenic progenitors; c) microvascular-associated
contractile cells (i.e., pericytes), which may fuse directly with myofibers. The proposed studies aim to: 1)
characterize myogenic-specific marker expression by cells in the satellite cell and interstitium niches of
EOMs versus limb and diaphragm muscles; 2) compare growth and renewal potential of myogenic stem
and progenitor cells in EOMs versus limb and diaphragm muscles; 3) investigate the potential of donor
satellite cells and pericytes from EOMs versus limb and diaphragm muscles to contribute to in vivo
muscle repair. Cells from wildtype and dystrophin-null mice that carry various reporter genes (for tracing
the different cell types and their progeny) will be investigated in vivo and in culture. The expected results
of the proposed studies will contribute to a better understanding of the cellular milieu that supports EOM
maintenance in adult life and will provide new insights regarding the role of microvasculature-associated
cells in skeletal myogenesis. Further characterization of EOM myogenic progenitors is essential for
developing repair strategies to treat extraocular muscle disorders. The proposed studies will also shed
new light on the functional status of myogenic progenitors in aging and dystrophin-deficient muscles,
providing important information for muscle rehabilitation strategies.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Isolation of Mouse Periocular Tissue for Histological and Immunostaining Analyses of the Extraocular Muscles and Their Satellite Cells.
分离小鼠眼周组织,用于眼外肌及其卫星细胞的组织学和免疫染色分析。
DOI:
10.1007/978-1-4939-3810-0_9
发表时间:
2016
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
作者:
[Stuelsatz,Pascal, Yablonka-Reuveni,Zipora]
通讯作者:
Yablonka-Reuveni,Zipora
EOM satellite cells for DMD therapy
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批准号:9087364
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海外基金