Infusible Extracellular Matrix for Treating Myocardial Infarction
可溶性细胞外基质治疗心肌梗塞
基本信息
- 批准号:10642880
- 负责人:
- 金额:$ 73.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-10 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:Acute myocardial infarctionAgingAlternative TherapiesAnimalsApoptosisArrhythmiaBalloon AngioplastyBindingBiocompatible MaterialsCardiacCardiac MyocytesCathetersCause of DeathCell SurvivalCell TherapyCellsChronicClinicalDevelopmentEchocardiographyEligibility DeterminationEndothelial CellsEndotheliumExtracellular MatrixFamily suidaeFibrosisFunctional disorderGeometryGerm CellsGoalsHeartHeart failureHistologicHistologyHolter ElectrocardiographyHydrogelsImmuneImmunohistochemistryInfiltrationInfusion proceduresInjectableInjectionsInterventionIntravenousKnowledgeLeadLeftLeft Ventricular FunctionLiquid substanceMagnetic Resonance ImagingMediatingMeta-AnalysisMetabolismModelingMyocardialMyocardial InfarctionMyocardiumPatientsPhase I Clinical TrialsPhenotypePorosityPre-Clinical ModelRattusRegenerative MedicineReperfusion TherapyRestRouteSafetyTechnologyTemperatureTherapy trialTissue EngineeringTissuesTreatment EfficacyVascular PermeabilitiesVentricularWestern WorldWorkagedcardiac repaircostcytokinehealingheart functionimmune cell infiltrateimmunoregulationimprovedminimally invasiveneovascularizationnovel therapeuticspolarized cellreceptorregeneration potentialrepairedresponsescaffoldsexsingle-cell RNA sequencingtranscriptomicstranslational study
项目摘要
Summary
Despite recent advances in tissue engineering and regenerative medicine, heart failure (HF) following myocardial
infarction (MI) continues to be the leading cause of death in the U.S., and the rest of the western world. One of
our goals is the development of new, minimally invasive tissue-engineered therapies for the treatment of MI.
While cell therapies have been extensively studied for the treatment of MI and HF, meta-analyses of initial cell
therapy trials suggest only a modest effect on cardiac function. Injectable biomaterials that stimulate endogenous
repair are an attractive, potentially more effective alternative since therapies could still be delivered minimally
invasively via catheter, yet could be off the shelf and have significantly reduced costs and complications
compared to cell products. The PI’s lab developed the first cardiac specific injectable hydrogel, a myocardial
matrix hydrogel, which is derived from decellularized porcine myocardial extracellular matrix (ECM) and is
deliverable via a transendocardial injection catheter. This material is liquid at room temperature and forms a
porous and fibrous scaffold upon injection, which we have shown promotes pro-remodeling immune cell
polarization, other endogenous cell infiltration and cardiac repair in subacute and chronic MI models. This initial
work led to a successful Phase I clinical trial in post-MI patients. However, this approach is not amenable to
treating acute MI patients because of safety issues related to transendocardial injections. Therefore, significant
damage and remodeling of the heart will occur before a patient is even eligible for this therapy. In contrast to
transendocardial delivery, intracoronary infusion can be performed in acute MI patients as interventional
cardiologists are already performing a balloon angioplasty. We therefore recently developed a new infusible form
of ECM (iECM) that can be delivered via intracoronary infusion to coat and fill gaps of damaged vasculature to
heal the tissue. We have already shown this is effective when delivered immediately post-reperfusion in a rat
acute MI model and in a pilot pig study. In acute MI, we hypothesize that iECM promotes endothelial cell survival
and polarization of infiltrating immune cells to a pro-remodeling phenotype, which secondarily along with an
already demonstrated reduction in vascular permeability results in improved cardiomyocyte survival. Our
preliminary results provide strong support for the use of our new iECM technology for treating acute MI. In this
proposal, we will better understand the immunomodulatory and regenerative potential of our iECM technology
and perform translational studies with the goal of developing a novel therapy for acute MI.
总结
尽管最近在组织工程和再生医学方面取得了进展,但心肌梗死后心力衰竭(HF)仍是一个严重的问题。
梗死(MI)仍然是美国的主要死亡原因,和其他西方世界。之一
我们的目标是开发新的微创组织工程疗法来治疗心肌梗死。
虽然细胞疗法已被广泛研究用于治疗MI和HF,但初始细胞疗法的荟萃分析表明,
治疗试验表明对心脏功能只有适度的影响。刺激内源性的可注射生物材料
修复是一种有吸引力的、可能更有效的替代方案,因为治疗仍然可以最小限度地提供
通过导管侵入,但可以现成的,并显着降低成本和并发症
与细胞产品相比。PI的实验室开发了第一种心脏特异性可注射水凝胶,
基质水凝胶,其来源于脱细胞的猪心肌细胞外基质(ECM),
可通过经血管内注射导管输送。这种材料在室温下是液体,
多孔和纤维支架注射后,我们已经表明,促进促重塑免疫细胞
极化、其他内源性细胞浸润和心脏修复。该初始
这项工作导致了在心肌梗死后患者中成功的I期临床试验。然而,这种方法并不适用于
治疗急性心肌梗死患者,因为与经血管内注射相关的安全性问题。因此,重要的
心脏的损伤和重塑将在患者甚至有资格接受这种治疗之前发生。相比
在急性MI患者中,经血管内输送、冠状动脉内输注可作为介入性
心脏病专家已经在做球囊血管成形术了因此,我们最近开发了一种新的不溶性形式,
ECM(iECM),可通过冠状动脉内输注输送,以涂覆和填充受损血管的间隙,
治愈组织我们已经证明,在大鼠再灌注后立即给予这种药物是有效的。
急性心肌梗死模型和中试猪研究。在急性心肌梗死中,我们假设iECM促进内皮细胞存活,
以及浸润免疫细胞向促重塑表型的极化,其沿着
已经证实血管通透性的降低导致心肌细胞存活率的提高。我们
初步结果为使用我们的新iECM技术治疗急性MI提供了强有力的支持。在这
我们将更好地了解iECM技术的免疫调节和再生潜力
并进行转化研究,目的是开发急性心肌梗死的新疗法。
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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Karen L Christman其他文献
Karen L Christman的其他文献
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{{ truncateString('Karen L Christman', 18)}}的其他基金
Training in Bioengineering Research and Technology Development in Cardiovascular in Cardiopulmonary Health and Disease
心肺健康和疾病领域心血管生物工程研究和技术开发培训
- 批准号:
10614653 - 财政年份:2022
- 资助金额:
$ 73.57万 - 项目类别:
Infusible Extracellular Matrix for Treating Myocardial Infarction
可溶性细胞外基质治疗心肌梗死
- 批准号:
10504948 - 财政年份:2022
- 资助金额:
$ 73.57万 - 项目类别:
New infusible ECM hydrogel for treating acute myocardial infarction
新型可熔ECM水凝胶治疗急性心肌梗死
- 批准号:
9907247 - 财政年份:2020
- 资助金额:
$ 73.57万 - 项目类别:
Injectable Biomaterial for Treating Hypoplastic Left Heart Syndrome
用于治疗左心发育不全综合征的可注射生物材料
- 批准号:
10322051 - 财政年份:2019
- 资助金额:
$ 73.57万 - 项目类别:
MMP Responsive Nanoparticles for Treating Acute Myocardial Infarction
MMP 响应纳米颗粒治疗急性心肌梗死
- 批准号:
9761569 - 财政年份:2017
- 资助金额:
$ 73.57万 - 项目类别:
MMP responsive polymeric materials for treating acute myocardial infarction
MMP响应性高分子材料治疗急性心肌梗死
- 批准号:
10734728 - 财政年份:2017
- 资助金额:
$ 73.57万 - 项目类别:
Extracellular matrix hydrogels for treating ischemia
用于治疗缺血的细胞外基质水凝胶
- 批准号:
9210846 - 财政年份:2016
- 资助金额:
$ 73.57万 - 项目类别:
A 3-D biomimetic human islet to model beta cell function in health and disease
3D 仿生人类胰岛,用于模拟健康和疾病中 β 细胞的功能
- 批准号:
8813754 - 财政年份:2014
- 资助金额:
$ 73.57万 - 项目类别:
A 3-D biomimetic human islet to model beta cell function in health and disease
3D 仿生人类胰岛,用于模拟健康和疾病中 β 细胞的功能
- 批准号:
9169716 - 财政年份:2014
- 资助金额:
$ 73.57万 - 项目类别:
Extracellular matrix hydrogels for treating ischemia
用于治疗缺血的细胞外基质水凝胶
- 批准号:
8657106 - 财政年份:2012
- 资助金额:
$ 73.57万 - 项目类别:
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