Modulating Exosome Cargos and Surfaces for Precision Heart Repair
调节外泌体货物和表面以实现精密心脏修复
基本信息
- 批准号:9763797
- 负责人:
- 金额:$ 38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:Acute myocardial infarctionAnimal ModelAnimalsBehaviorCardiacCardiomyopathiesCardiovascular DiseasesCardiovascular systemCaringCell DeathCell TherapyCell TransplantationCell TransplantsCellsDevelopmentDiseaseEngineeringEnsureFailureFamily suidaeFunctional disorderFutureGoalsHeartHeart DiseasesHeart InjuriesHeart failureHistologyHomingHumanImpairmentIn VitroInjectionsInjuryIntravenousIschemiaLeadMAP2K1 geneMeasuresMediatingMedicalMicroRNAsModelingModificationMorbidity - disease rateMorphologyMusMyocardial InfarctionMyocardial dysfunctionN-octanoylglucosylamineNamesPTEN genePalliative CarePatientsPeptidesPropertyProteinsProto-Oncogene Proteins c-aktRNARecovery of FunctionRegenerative MedicineReperfusion TherapyRiskSignal PathwaySocietiesStandardizationStem cell transplantStem cellsStromal CellsSurfaceSurvivorsSystemTechniquesTestingTherapeuticTherapeutic AgentsThoracic Surgical ProceduresTimeTransplantationUnited StatesVesiclebasecardiac regenerationcardiac repaircell typeclinical translationexosomeexperienceexperimental studyfunctional losshealingin vivoknock-downloss of functionmortalitymouse modelneoplastic cellparacrinepreservationregenerativerepairedtherapeutic candidatetherapeutic miRNAtranscriptome sequencing
项目摘要
It has been established that most of the beneficial effects of transplanted cells are indirect:
injected cells secrete paracrine factors that promote endogenous heart repair. Among those
secreted substances, exosomes are 30-100 nm vesicles secreted by a wide range of cell types
including tumor cells and stem cells. Exosomes can transport microRNAs (miRs) that enable
cells to communicate with neighboring cells to change their behavior. The essential miR cargos
underlying the therapeutic potencies of exosomes have yet to be determined. In addition, unlike
stem cells, exosomes do not have migratory ability therefore local injections are performed to
ensure delivery. However, direction injection into the heart is not trivial, normally requiring open-
chest surgery or sophisticated endomyocardial injection setups such as the NOGA mapping
system. It is crucial to develop techniques to target systemically delivered exosomes to the
heart injury. Our long-term goal is to create exosomes with optimized cargos and surfaces for
precision cardiac repair. In our preliminary studies, we compared cultured cardiac stromal cells
from normal and failing human hearts, and isolated exosomes from these cells. In vitro
experiments and animal studies indicate an impaired regenerative activity of exosomes from
heart failure patients. In addition, miR array revealed dysregulation of miR-21 in heart failure
exosomes. Based on those preliminary results, we hypothesize that: i) there is a loss of
therapeutic properties in exosomes from heart failure and such functional loss is due to
alterations in repertoire miRs such as miR-21; ii) modulating such miR cargos could rescue the
regenerative potential of the diseased exosomes; iii) efficient systemic delivery and injury
targeting can be achieved by exosomal surface modification. Studies proposed in this proposal
are highly significant since they aim to enhance our fundamental understating of mechanisms
underlying exosomes' reparative function but may also pave the way for future clinical
translation.
已经确定,移植细胞的大部分有益效果是间接的:
注射的细胞分泌促进内源性心脏修复的旁分泌因子。人中
分泌物质,外泌体是由多种细胞类型分泌的30-100 nm囊泡
包括肿瘤细胞和干细胞。外泌体可以转运微RNA(miR),
细胞与相邻细胞通信以改变它们的行为。重要的miR货物
外来体的潜在治疗效力尚未确定。此外,与
干细胞、外来体不具有迁移能力,因此进行局部注射,
确保交付。然而,直接注射到心脏中并不是微不足道的,通常需要打开-
胸部手术或复杂的肌内膜注射设置,如NOGA标测
系统关键是开发将全身递送的外泌体靶向至肿瘤细胞的技术。
心脏损伤我们的长期目标是创造具有优化的货物和表面的外泌体,
精确的心脏修复在我们的初步研究中,我们比较了培养的心脏基质细胞,
从正常和衰竭的人类心脏中,并从这些细胞中分离出外泌体。体外
实验和动物研究表明,来自哺乳动物的外来体的再生活性受损,
心力衰竭患者。此外,miR阵列揭示了心力衰竭中miR-21的失调
外来体基于这些初步结果,我们假设:i)有一个损失,
在来自心力衰竭的外来体中的治疗性质,并且这种功能丧失是由于
i)改变所有库miR如miR-21; ii)调节此类miR货物可以挽救miR-21的表达。
患病外泌体的再生潜力; iii)有效的全身递送和损伤
靶向可以通过外泌体表面修饰来实现。本提案中提议的研究
是非常重要的,因为它们旨在加强我们对机制的基本理解,
潜在的外泌体的修复功能,但也可能为未来的临床
翻译.
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Ke Cheng其他文献
Ke Cheng的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Ke Cheng', 18)}}的其他基金
Drug Delivery and Biomimetic Approaches for Optimal Stem Cell Therapy
最佳干细胞治疗的药物输送和仿生方法
- 批准号:
10370380 - 财政年份:2021
- 资助金额:
$ 38万 - 项目类别:
Drug Delivery and Biomimetic Approaches for Optimal Stem Cell Therapy
最佳干细胞治疗的药物输送和仿生方法
- 批准号:
10995606 - 财政年份:2021
- 资助金额:
$ 38万 - 项目类别:
Surgical Microneedle Patch Delivery of CMMP for Heart Repair
外科微针贴片输送 CMMP 用于心脏修复
- 批准号:
9982489 - 财政年份:2020
- 资助金额:
$ 38万 - 项目类别:
Surgical Microneedle Patch Delivery of CMMP for Heart Repair
外科微针贴片输送 CMMP 用于心脏修复
- 批准号:
10586112 - 财政年份:2020
- 资助金额:
$ 38万 - 项目类别:
Surgical Microneedle Patch Delivery of CMMP for Heart Repair
外科微针贴片输送 CMMP 用于心脏修复
- 批准号:
10396023 - 财政年份:2020
- 资助金额:
$ 38万 - 项目类别:
Cardiac Patches Loaded with Stem Cell Factors to Treat Heart Failure
含有干细胞因子的心脏贴片可治疗心力衰竭
- 批准号:
10229460 - 财政年份:2019
- 资助金额:
$ 38万 - 项目类别:
Modulating Exosome Cargos and Surfaces for Precision Heart Repair
调节外泌体货物和表面以实现精密心脏修复
- 批准号:
10393509 - 财政年份:2019
- 资助金额:
$ 38万 - 项目类别:
Harnessing Platelet-Endothelial Interactions for Exosome Delivery
利用血小板-内皮相互作用进行外泌体递送
- 批准号:
10669452 - 财政年份:2019
- 资助金额:
$ 38万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 38万 - 项目类别:
Grant-in-Aid for Early-Career Scientists