Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosis
将间充质基质细胞封装在工程微凝胶中以解决肺纤维化
基本信息
- 批准号:10598507
- 负责人:
- 金额:$ 39.98万
- 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 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAlginatesAntibodiesBiochemicalBiocompatible MaterialsBiomedical EngineeringBiophysicsCell TherapyCellsChronicCicatrixCollagenCuesDataDendritic CellsDendritic cell activationDepositionDiagnosisDiseaseDisease modelEncapsulatedEngineeringExtracellular MatrixFibrosisGelGeneticGlycocalyxHydrogelsImmuneImpairmentInflammatoryInjuryInterstitial CollagenaseLigandsLungMicrofluidicsModelingMusOrganPathogenesisPathway interactionsPhenotypeProductionPropertyPulmonary FibrosisRGD (sequence)Receptors, Tumor Necrosis Factor, Type IIResearch PersonnelResolutionRoleTNF geneTNFRSF1A geneTNFRSF1B geneTechnologyTestingTherapeuticThinnessTimeTissuesTransplantationTumor Necrosis Factor ActivationTumor Necrosis Factor ReceptorWorkbiophysical techniquescollagenasecurative treatmentscytokinedesigneffective therapyidiopathic pulmonary fibrosisimprovedin vivoin vivo evaluationknock-downmembermesenchymal stromal cellmultidisciplinarynovelpreventprogramspublic health relevancepulmonary functionresidenceresponsescreeningstem cells
项目摘要
PROJECT SUMMARY
The ability of mesenchymal stromal cells (MSCs) to adapt to their tissue niche and remodel extracellular matrix
(ECM) could be therapeutically beneficial in treating fibrotic diseases. However, leveraging this property has
been challenging because MSCs are rapidly cleared from tissue once delivered. Thus, specific pathways to
induce MSCs to remodel the ECM and the utility of these remain unclear. We described herein a highly
efficient approach to encapsulate single cells in engineered microgels with predefined biochemical and
biophysical cues. We have fine-tuned this approach to show that clearance of MSCs is significantly delayed
when they are delivered in thin microgels intratracheally to lungs. Importantly, our preliminary data show that
this treatment decreases collagen accumulation in a murine lung fibrosis model. We show in these supporting
studies amplified ability of MSCs to degrade collagen-I when the cells are encapsulated in engineered
hydrogels with tunable stiffness. In this my first RO1 proposal, I will build upon these results to test the
hypothesis that programming of MSCs using specifically engineered microgels activates the potential of MSCs
to promote resolution of fibrosis and thus restore lung function. In Aim 1, we will determine the role of
microencapsulation in controlling retention of MSCs in lungs and facilitating resolution of lung fibrosis. In Aim 2,
we will determine the potentially important role of the inflammatory cytokine tumor necrosis factor-α (TNFα) in
modifying the phenotype of microencapsulated MSCs to produce high amounts collagenases with enhanced
potential to resolve lung fibrosis. We predict that selectively activating TNF receptor 2 in MSCs encapsulated in
soft microgels can resolve lung fibrosis. The project is highly multidisciplinary in that it will employ a
combination of expertise in biomaterials, lung fibrosis, biophysical, genetic, and mouse in vivo approaches to
address the specific aims. The results will help to define how MSCs can facilitate resolution of fibrosis through
prolonging their in vivo residence time in lungs, and modifying their phenotype through encapsulation in
engineered and tunable microgels to optimize their production of collagenases. We thus hope to develop novel
MSC based approaches to remodel aberrant extracellular matrix and to treat lung fibrosis.
!
项目总结
间充质基质细胞适应其组织生态位和重塑细胞外基质的能力
(ECM)在治疗纤维化疾病方面可能是有益的。然而,利用这一属性
一直具有挑战性,因为骨髓间充质干细胞一旦被输送就能迅速从组织中清除。因此,具体的途径是
诱导MSCs重塑ECM,其效用尚不清楚。我们在这里描述了一种高度
一种高效的将单个细胞包裹在具有预定义的生物化学和
生物物理线索。我们已经对这种方法进行了微调,以表明MSCs的清除明显延迟
当它们以薄的微凝胶形式通过气管进入肺部时。重要的是,我们的初步数据显示
这种治疗方法减少了小鼠肺纤维化模型中的胶原堆积。我们在这些支持中展示了
当细胞被包裹在工程材料中时,研究增强了MSCs降解I型胶原的能力
硬度可调的水凝胶。在我的第一个RO1提案中,我将在这些结果的基础上测试
假设使用特定工程的微凝胶编程MSCs可以激活MSCs的潜能
促进纤维化消退,从而恢复肺功能。在目标1中,我们将确定
微胶囊在控制MSCs在肺内滞留和促进肺纤维化消退中的作用。在目标2中,
我们将确定炎性细胞因子肿瘤坏死因子-α(肿瘤坏死因子α)在
改良微囊化间充质干细胞的表型以产生高量胶原酶
有可能解决肺纤维化。我们预测选择性激活被包裹的MSCs中的肿瘤坏死因子受体2
软性微凝胶可消解肺纤维化。该项目是高度多学科的,因为它将雇用一名
结合生物材料、肺纤维化、生物物理学、遗传学和小鼠体内方法的专业知识
解决具体目标。这一结果将有助于确定骨髓间充质干细胞如何通过
延长其在肺内的体内滞留时间,并通过包埋改变其表型。
经过改造和可调的微凝胶,以优化胶原酶的生产。因此,我们希望开发小说
基于MSC的重建异常细胞外基质和治疗肺纤维化的方法。
好了!
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.
- DOI:10.1007/s13346-022-01189-4
- 发表时间:2023-08
- 期刊:
- 影响因子:5.4
- 作者:Dozzo, Annachiara;Galvin, Aoife;Shin, Jae-Won;Scalia, Santo;O'Driscoll, Caitriona M.;Ryan, Katie B.
- 通讯作者:Ryan, Katie B.
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Jae-Won Shin其他文献
Jae-Won Shin的其他文献
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{{ truncateString('Jae-Won Shin', 18)}}的其他基金
Engineering microscale hydrogel deposition to direct single stem cell differentiation
工程微型水凝胶沉积指导单干细胞分化
- 批准号:
10370437 - 财政年份:2021
- 资助金额:
$ 39.98万 - 项目类别:
Engineering microscale hydrogel deposition to direct single stem cell differentiation
工程微型水凝胶沉积指导单干细胞分化
- 批准号:
10181469 - 财政年份:2021
- 资助金额:
$ 39.98万 - 项目类别:
Engineering microscale hydrogel deposition to direct single stem cell differentiation
工程微型水凝胶沉积指导单干细胞分化
- 批准号:
10548197 - 财政年份:2021
- 资助金额:
$ 39.98万 - 项目类别:
Engineering microscale hydrogel deposition to direct single stem cell differentiation
工程微型水凝胶沉积指导单干细胞分化
- 批准号:
10582026 - 财政年份:2021
- 资助金额:
$ 39.98万 - 项目类别:
Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosis
将间充质基质细胞封装在工程微凝胶中以解决肺纤维化
- 批准号:
10132377 - 财政年份:2019
- 资助金额:
$ 39.98万 - 项目类别:
Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosis
将间充质基质细胞封装在工程微凝胶中以解决肺纤维化
- 批准号:
10372942 - 财政年份:2019
- 资助金额:
$ 39.98万 - 项目类别:
Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosis
将间充质基质细胞封装在工程微凝胶中以解决肺纤维化
- 批准号:
9894836 - 财政年份:2019
- 资助金额:
$ 39.98万 - 项目类别:
Mechanically controlled release of hematopoietic factors from mesenchymal stromal cells for blood regeneration
机械控制间充质基质细胞释放造血因子用于血液再生
- 批准号:
8805621 - 财政年份:2014
- 资助金额:
$ 39.98万 - 项目类别:
Mechanically controlled release of hematopoietic factors from mesenchymal stromal cells for blood regeneration
机械控制间充质基质细胞释放造血因子用于血液再生
- 批准号:
8979703 - 财政年份:2014
- 资助金额:
$ 39.98万 - 项目类别:
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