Enhanced Myocardial Repair with CardioClusters and CardioChimeras
利用 CardioClusters 和 CardioChimeras 增强心肌修复
基本信息
- 批准号:8675146
- 负责人:
- 金额:$ 37.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-05-01 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:Acute myocardial infarctionAdoptive TransferAllogenicAnti-Inflammatory AgentsAnti-inflammatoryApoptosisAutologousBlood VesselsCardiacCardiac MyocytesCardiovascular systemCell DeathCell Differentiation processCell LineCell ProliferationCell SurvivalCell TherapyCell fusionCellsCharacteristicsCicatrixClinicalClinical TrialsCoculture TechniquesCommitCommunicationDiseaseEngineeringEngraftmentExhibitsExtracellular Matrix ProteinsFailureGenetic MaterialsGoalsGrowthGrowth FactorHealthcare SystemsHeartHeart DiseasesHeart failureHumanHybridsHypoxiaIndividualInflammationInjection of therapeutic agentInjuryKnowledgeMalignant NeoplasmsMediatingMesenchymal Stem CellsMeta-AnalysisMethodsMonitorMuscle CellsMyocardialMyocardial InfarctionMyocardiumNatural regenerationOutputPatientsPatternPopulationPreventionPropertyPublic HealthRelative (related person)SafetySmooth Muscle MyocytesSolutionsStem cellsStimulusStructureSuspension substanceSuspensionsTestingTissuesUnited Statesangiogenesisbasecardiac repaircell behaviorcell growthcell typeclinically relevantcombinatorialcytokinefallshuman stem cellsimprovedinnovationinsightmortalitymuscular structurenovelparacrinepublic health relevanceregenerativerepairedrestorationstemstem cell population
项目摘要
DESCRIPTION (provided by applicant): Regenerative capacity of the heart is mediated through multiple distinct populations of stem cell types that are the subject of ongoing intense study. In the past decade, isolation and characterization of cardiac progenitor cells (CPCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) has provided substantial insight to the capabilities of stem cells to rebuild the damaged heart and advance clinical therapy. Clinical trials have proven the efficacy and safety of autologous and allogeneic CPC and MSC delivery to human patients, yet improvements in cardiac function and reduction in scar tissue remain modest and far below that needed for restoration of normal functional output. This proposal overcomes these current cell- based limitations with two novel methods for improving myocardial repair: 1) CardioClusters, a three- dimensional microenvironment consisting of CPCs, MSCs and EPCs, and 2) CardioChimeras, the product of cellular fusion between two stem cell populations. The innovation of this proposal is the creation of CardioClusters and CardioChimeras with the ability to capitalize upon beneficial attributes of multiple human stem cells from a single patient providing a clinically relevant translational strategy. The short-term goal of this proposal will determine the enhanced proliferation, growth, survival and commitment potential of CardioChimeras and stem cells in CardioClusters, which are optimized for improving cell-based therapy. Accomplishing the stated aims of this proposal will yield the construction and comprehensive characterization of CardioClusters and CardioChimeras. Specific Aims are: 1) CardioClusters exhibit enhanced proliferation, survival and cardiac commitment relative to cardiospheres, single or combinatorial cell populations, 2) CardioChimeras display improved characteristics of growth, survival, secretion of paracrine factors and cardiac commitment relative to non-fused cell populations and 3) CardioClusters as well as CardioChimeras restore myocardial structure and function after intramyocardial injection better than cardiospheres or single / multiple cell suspensions. The significance of these studies is to create novel cell-based strategies engineered to improve current cellular therapy to mitigate ischemic disease. Collectively, studies in this proposal will pave the way for interventional approaches to selectively adapt stem cell behavior and merge beneficial attributes of stem cell populations found within the human heart for prevention of heart failure after cardiomyopathic injury.
描述(由申请人提供):心脏的再生能力是通过多种不同的干细胞类型介导的,这些干细胞类型是正在进行的激烈研究的主题。在过去的十年中,心脏祖细胞(CPCs)、间充质干细胞(MSCs)和内皮祖细胞(EPCs)的分离和表征为干细胞重建受损心脏和推进临床治疗的能力提供了实质性的见解。临床试验已经证明了自体和同种异体CPC和MSC输送给人类患者的有效性和安全性,但心功能的改善和疤痕组织的减少仍然是适度的,远远低于恢复正常功能输出所需的水平。本研究提出了两种改善心肌修复的新方法,克服了目前基于细胞的局限性:1)CardioClusters,一种由心肌干细胞、间充质干细胞和EPCs组成的三维微环境;2)CardioChimeras,两种干细胞群体之间细胞融合的产物。这一提议的创新之处在于心脏集群和心脏嵌合体的创造,它们能够利用来自单个患者的多个人类干细胞的有益属性,提供临床相关的转化策略。该提案的短期目标将确定心脏嵌合体和干细胞在心脏簇中的增殖、生长、存活和承诺潜力,这些都是优化的,可以改善细胞治疗。完成本提案的既定目标将产生心脏簇和心脏嵌合体的构建和全面表征。具体目标是:1)与心球细胞、单个或组合细胞群相比,心细胞簇具有更强的增殖、存活和心脏承受力;2)心嵌合体具有更好的生长、存活、与非融合细胞群和3)心肌内注射相比,心肌球或单/多细胞悬浮液能更好地恢复心肌结构和功能。这些研究的意义在于创造新的基于细胞的策略,以改进当前的细胞治疗来减轻缺血性疾病。总的来说,本提案中的研究将为选择性适应干细胞行为的介入方法铺平道路,并合并人类心脏中发现的干细胞群体的有益属性,以预防心肌病损伤后的心力衰竭。
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(1)
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 }}
MARK ALAN SUSSMAN其他文献
MARK ALAN SUSSMAN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('MARK ALAN SUSSMAN', 18)}}的其他基金
Next Generation Regenerative Therapy with Pim-1 Enhanced Cardiac Progenitor Cells
使用 Pim-1 增强型心脏祖细胞的下一代再生疗法
- 批准号:
9352458 - 财政年份:2017
- 资助金额:
$ 37.38万 - 项目类别:
Enhanced Myocardial Repair with CardioClusters and CardioChimeras
利用 CardioClusters 和 CardioChimeras 增强心肌修复
- 批准号:
9266810 - 财政年份:2014
- 资助金额:
$ 37.38万 - 项目类别:
Enhanced Myocardial Repair with CardioClusters and CardioChimeras
利用 CardioClusters 和 CardioChimeras 增强心肌修复
- 批准号:
9041013 - 财政年份:2014
- 资助金额:
$ 37.38万 - 项目类别:
Beta-adrenergic signaling: double edged sword of myocardial repair
β-肾上腺素能信号传导:心肌修复的双刃剑
- 批准号:
8431986 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
Beta-adrenergic signaling: double edged sword of myocardial repair
β-肾上腺素能信号传导:心肌修复的双刃剑
- 批准号:
8790766 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
Cardioprotection by optimizing mTOR activity
通过优化 mTOR 活性来保护心脏
- 批准号:
8446101 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
Cardioprotection by optimizing mTOR activity
通过优化 mTOR 活性来保护心脏
- 批准号:
8792404 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
Beta-adrenergic signaling: double edged sword of myocardial repair
β-肾上腺素能信号传导:心肌修复的双刃剑
- 批准号:
8996702 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
Cardioprotection by optimizing mTOR activity
通过优化 mTOR 活性来保护心脏
- 批准号:
8620713 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
Beta-adrenergic signaling: double edged sword of myocardial repair
β-肾上腺素能信号传导:心肌修复的双刃剑
- 批准号:
8620715 - 财政年份:2013
- 资助金额:
$ 37.38万 - 项目类别:
相似海外基金
Time to ATTAC: Adoptive Transfer of T cells Against gp100+ Cells to treat LAM
ATTAC 时间:针对 gp100 细胞的 T 细胞过继转移来治疗 LAM
- 批准号:
10682121 - 财政年份:2023
- 资助金额:
$ 37.38万 - 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
- 批准号:
10576370 - 财政年份:2022
- 资助金额:
$ 37.38万 - 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
- 批准号:
10387023 - 财政年份:2022
- 资助金额:
$ 37.38万 - 项目类别:
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
- 批准号:
10248409 - 财政年份:2019
- 资助金额:
$ 37.38万 - 项目类别:
A phase I clinical study of adoptive transfer of regulatory T cells (Tregs) and low-dose interleukin-2 (IL-2) for the treatment of chronic graft-versus-host disease (GVHD): gene-marking to inform rational combination therapy
调节性 T 细胞 (Treg) 和低剂量白细胞介素 2 (IL-2) 过继转移治疗慢性移植物抗宿主病 (GVHD) 的 I 期临床研究:基因标记为合理的联合治疗提供信息
- 批准号:
nhmrc : GNT1163111 - 财政年份:2019
- 资助金额:
$ 37.38万 - 项目类别:
Project Grants
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
- 批准号:
10462684 - 财政年份:2019
- 资助金额:
$ 37.38万 - 项目类别:
Gene edited lymphoid progenitors for adoptive transfer as a treatment of primary immunodeficiency
基因编辑的淋巴祖细胞用于过继转移作为原发性免疫缺陷的治疗
- 批准号:
398018062 - 财政年份:2018
- 资助金额:
$ 37.38万 - 项目类别:
Research Grants
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
- 批准号:
9308643 - 财政年份:2017
- 资助金额:
$ 37.38万 - 项目类别:
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
- 批准号:
9447149 - 财政年份:2017
- 资助金额:
$ 37.38万 - 项目类别:
Targeting Cancer miRNAs by Adoptive Transfer of Programmed B Lymphocytes
通过程序化 B 淋巴细胞的过继转移靶向癌症 miRNA
- 批准号:
8893915 - 财政年份:2014
- 资助金额:
$ 37.38万 - 项目类别: