Characterization of Cell-Based Therapy for Congenital Heart Patients
先天性心脏病患者细胞疗法的特征
基本信息
- 批准号:7922572
- 负责人:
- 金额:$ 12.91万
- 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
- 起止时间:2009-09-01 至 2014-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAgeAnatomic SitesAnimal ModelApoptosisAutologousAwardBiologyBone MarrowCardiacCardiac MyocytesCardiomyopathiesCardiovascular systemCell TherapyCellsCessation of lifeCharacteristicsChildChildhoodChronicClinical ProtocolsClinical TrialsCongenital Heart DefectsCoronary VesselsDataDefectDevelopmentDiagnosisDifferentiation and GrowthDoxorubicinFunctional disorderFundingFutureGeneric DrugsGrantGrowthHeartHeart TransplantationHeart failureHumanHuman CharacteristicsIn VitroInfantInferiorLifeLife ExpectancyLocationMedicalMentorsModelingMolecular BiologyMolecular Biology TechniquesMulti-Institutional Clinical TrialMyocardialMyocardial InfarctionMyocardial IschemiaMyocardiumMyofibrilsNatural regenerationOnly ChildOperative Surgical ProceduresPathologicPatientsPhenotypePhysiologicalPopulationPrincipal InvestigatorPropertyRegenerative MedicineResearchResearch SupportSourceStem cell transplantStem cellsTechniquesTestingTherapeutic UsesTrainingTransplantationUniversitiesVentricular Dysfunctioncareerclinical applicationcongenital heart disorderdesignexperiencefunctional losshuman tissuein vivonovelregenerativerepairedresearch studyself-renewalstem cell biologytool
项目摘要
This grant is a K08 Mentored Career Developmental Award submission supporting the research of Dr. Sunjay Kaushal. To advance his career in stem cell based therapy for congenital heart patients, this grant incorporates training in two vital fields: (1) molecular biology techniques (isolation and characterization of cardiac stem cells, immunohistiochemistry) and (2) in vivo transplantation techniques. Both of these fields is absent from Dr. Kaushal's previous training, yet are vital in advancing research in this field. Dr. Kaushal's mentor is Dr. Doug Losordo at Northwestern University who has an extensive research experience in this field. Recent evidence has identified a population of cells within the heart itself as a potential autologous cell source for cellular regeneration, termed cardiac stem cells (CSCs). As of yet, the clinical application of these CSCs for pediatric patients who develop non-ischemic cardiomyopathies is unclear. To accomplish this objective, we will have three Specific Aims which follow a progressive sequence. Aims 1 and 2 center on the accrual of detailed descriptive properties of the growth, self-renewal potential, and myocardial differentiation characteristics of hCSCs from different anatomic sites of the heart. In addition, we will determine whether age or the pathologic state of the patient affects the innate properties of the hCSCs. The in vivo analysis will involve examining quantitative and qualitative myocardial regeneration in a doxorubicin-induced cardiomyopathy model, which replicates many of the salient features of cardiomyopathy present in our children with heart failure. Once we have established whether the human myocardium maintains a generic CSC or, in contrast, a more cardiac chamber-specific CSC, which may be influenced by age and physiologic state, we will test the best identified CSC to determine whether it is superior, inferior, or equal to bone marrow-derived cells for the regeneration of cardiomyocytes and coronary vessels in the doxorubicin- induced cardiomyopathy model. We strongly believe that elucidating these issues is critical to constructing the most powerful regenerative clinical protocol. RELEVANCE (See instmctions): Since all of the experiments in this proposal involve human tissues, there will be very strong translational conclusions that will directly impact the development of future clinical trials. Furthermore, these experiments have direct clinical applications to patients who have congenital heart defects as these patients are living longer, and some develop cardiac dysfunction that may benefit from a cell-based therapy using hCSCs.
这项资助是K08指导职业发展奖提交的,支持Sunjay Kaushal博士的研究。为了推进他在先天性心脏病患者干细胞治疗方面的事业,该资助包括两个重要领域的培训:(1)分子生物学技术(心脏干细胞的分离和表征,免疫组织化学)和(2)体内移植技术。这两个领域在Kaushal博士之前的培训中都没有,但对于推进该领域的研究至关重要。Kaushal博士的导师是西北大学的Doug Losordo博士,他在这一领域拥有丰富的研究经验。最近的证据表明,心脏内部的细胞群是细胞再生的潜在自体细胞来源,称为心脏干细胞(CSCs)。到目前为止,这些CSCs在儿童非缺血性心肌病患者中的临床应用尚不清楚。为了实现这一目标,我们将有三个具体目标,它们遵循一个渐进的顺序。目的1和目的2集中在心脏不同解剖部位的hCSCs的生长、自我更新潜能和心肌分化特征的详细描述特性的积累。此外,我们将确定患者的年龄或病理状态是否会影响造血干细胞的先天特性。体内分析将包括在阿霉素诱导的心肌病模型中检测定量和定性心肌再生,该模型复制了我们的心衰儿童心肌病的许多显著特征。一旦我们确定了人类心肌是否维持一种通用的CSC,或者相反,一种可能受年龄和生理状态影响的更具心室特异性的CSC,我们将测试最佳识别的CSC,以确定在阿霉素诱导的心肌病模型中,它在心肌细胞和冠状血管再生方面是否优于、劣于或等于骨髓来源的细胞。我们坚信,阐明这些问题对于构建最强大的再生临床方案至关重要。相关性:由于本提案中的所有实验都涉及人体组织,因此将会有非常强有力的转化结论,这将直接影响未来临床试验的发展。此外,这些实验对先天性心脏缺陷患者有直接的临床应用,因为这些患者寿命更长,一些患者会出现心功能障碍,这些患者可能受益于hCSCs的细胞治疗。
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(2)
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Sunjay Kaushal其他文献
Sunjay Kaushal的其他文献
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{{ truncateString('Sunjay Kaushal', 18)}}的其他基金
Hyperglycemia of Maternal Diabetes Induces Cardiac Isl1 Positive Progenitor Dysfunction Leading to Heart Defects
母亲糖尿病引起的高血糖会导致心脏 Isl1 阳性祖细胞功能障碍,从而导致心脏缺陷
- 批准号:
10687863 - 财政年份:2020
- 资助金额:
$ 12.91万 - 项目类别:
Hyperglycemia of Maternal Diabetes Induces Cardiac Isl1 Positive Progenitor Dysfunction Leading to Heart Defects
母亲糖尿病引起的高血糖会导致心脏 Isl1 阳性祖细胞功能障碍,从而导致心脏缺陷
- 批准号:
10464979 - 财政年份:2020
- 资助金额:
$ 12.91万 - 项目类别:
Hyperglycemia of Maternal Diabetes Induces Cardiac Isl1 Positive Progenitor Dysfunction Leading to Heart Defects
母亲糖尿病引起的高血糖会导致心脏 Isl1 阳性祖细胞功能障碍,从而导致心脏缺陷
- 批准号:
10249305 - 财政年份:2020
- 资助金额:
$ 12.91万 - 项目类别:
Hyperglycemia of Maternal Diabetes Induces Cardiac Isl1 Positive Progenitor Dysfunction Leading to Heart Defects
母亲糖尿病引起的高血糖会导致心脏 Isl1 阳性祖细胞功能障碍,从而导致心脏缺陷
- 批准号:
10026655 - 财政年份:2020
- 资助金额:
$ 12.91万 - 项目类别:
Characterization of the Cardiac Progenitor Cell Exosomes for Optimal Therapeutics
心脏祖细胞外泌体的表征以实现最佳治疗
- 批准号:
10467907 - 财政年份:2019
- 资助金额:
$ 12.91万 - 项目类别:
The Role of C-Kit Positive Cardiac Progenitors in Maternal Diabetes-Induced Heart Defects and the Therapeutic Values of These Cells
C-Kit 阳性心脏祖细胞在母亲糖尿病引起的心脏缺陷中的作用以及这些细胞的治疗价值
- 批准号:
9403962 - 财政年份:2017
- 资助金额:
$ 12.91万 - 项目类别:
Mechanism of transplanted neonatal cardiac progenitor cells to repair ischemic myocardium
移植新生儿心脏祖细胞修复缺血心肌的机制
- 批准号:
10117849 - 财政年份:2014
- 资助金额:
$ 12.91万 - 项目类别:
Biological Characterization of Cardiac Stem Cells
心脏干细胞的生物学特性
- 批准号:
9249960 - 财政年份:2014
- 资助金额:
$ 12.91万 - 项目类别:
Biological Characterization of Cardiac Stem Cells
心脏干细胞的生物学特性
- 批准号:
8840316 - 财政年份:2014
- 资助金额:
$ 12.91万 - 项目类别:
Biological Characterization of Cardiac Stem Cells
心脏干细胞的生物学特性
- 批准号:
9042032 - 财政年份:2014
- 资助金额:
$ 12.91万 - 项目类别:
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