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
基本信息
- 批准号:10181469
- 负责人:
- 金额:$ 40.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAblationAddressAlginatesAnimal ModelBiocompatible MaterialsBiologicalBiological AssayBiophysicsBone RegenerationCell TherapyCell VolumesCellsClinicalClinical TrialsCuesDataDepositionDiseaseElasticityEncapsulatedEngineeringFormulationGelGene Expression ProfilingGeneticGenetic TranscriptionGrowthHeterogeneityHydrogelsImageIndividualInjectionsIntegrinsIon ChannelKineticsLigandsMarrowMeasuresMechanicsMediatingMembraneMembrane PotentialsMesenchymal Stem CellsMicrofluidicsNatural regenerationOsteogenesisOutcomePathway AnalysisPopulationProductionPropertyRGD (sequence)ReportingReproducibilityResearch PersonnelRoleSmall Interfering RNAStressTechnologyTestingTherapeuticThickThinnessTissuesValidationVanilloidWorkadult stem cellbasebiophysical modelbiophysical techniquesclinical efficacyclinically relevantdesignfos-related antigen 1imaging modalityimprovedin vivoinjuredinsightinstrumentationinterdisciplinary approachknock-downmathematical modelmembermouse modelmultidisciplinarynovelosteogenicprogramspublic health relevancereceptorregenerativeresponsestem cell differentiationstem cell fatestem cell functionstem cell growthstem cellstherapy outcometissue regenerationtranscription factortranscriptomeviscoelasticity
项目摘要
PROJECT SUMMARY
Adult stem cells hold broad-ranging clinical potential to regenerate injured tissues. For instance, mesenchymal
stem cells (MSCs) have been investigated in over 950 clinical trials for use in many disease indications.
Despite their significant clinical relevance, however, there is currently lack of the mechanistic understanding to
precisely control MSC functions for reproducible therapeutic outcomes. Engineered hydrogels have been used
to reveal the ability of MSCs to sense and respond to matrix biophysical cues, which subsequently impact the
differentiation potential of MSCs. However, leveraging these insights for therapeutic purposes has been
challenging, since current approaches to interface a cell population with a hydrogel by uncontrolled mixing
overlook the significance of heterogeneity in the local amount of the gel presented to individual cells, leading to
variable and unclear cell-material interactions at the single cell level. We describe herein a highly efficient
approach to control microscale hydrogel deposition around single cells in a 3D space independently of gel
composition and elasticity. Using this approach, our preliminary data show that MSCs rapidly expand in volume
when they adhere to an integrin ligand in thinner gels. We show that encapsulating single MSCs in a thin gel
coating is sufficient to enhance the osteogenic potential of MSCs even when gel elasticity is low. We will build
upon these results to test the hypothesis that controlling local gel deposition around single MSCs impacts
membrane tension and lineage specification by regulating cell volume expansion. In Aim 1, we will determine
the effect of varying local gel deposition on regulatory volume decrease by modulating mechanosensitive ion
channels and its impact on membrane tension of MSCs. In Aim 2, we will determine how varied local gel
deposition impacts single MSC fate and MSC-based bone regeneration. We predict that there exists a
transcriptional program that is selectively activated when the gel deposition becomes thinner, thereby
impacting lineage specification of MSCs independently of gel elasticity. The project is highly multidisciplinary in
that it will employ a combination of expertise in biomaterials, biophysical, genetic, and in vivo approaches to
address the specific aims. The results will help to define local gel deposition as an important determinant of
stem cell growth, thereby impacting stem cell mechanics and fate. Given the clinical relevance of these cells,
our results will inform formulation design of MSC-based therapeutics for improved regenerative outcomes.
项目概要
成体干细胞具有广泛的临床潜力,可以再生受损组织。例如,间充质
干细胞 (MSC) 已在超过 950 项临床试验中进行了研究,可用于多种疾病适应症。
然而,尽管它们具有重要的临床意义,但目前仍缺乏对其机制的理解。
精确控制 MSC 功能以获得可重复的治疗结果。工程水凝胶已被使用
揭示 MSC 感知和响应基质生物物理线索的能力,从而影响
MSCs的分化潜能。然而,利用这些见解来达到治疗目的已经
具有挑战性,因为目前通过不受控制的混合将细胞群与水凝胶连接的方法
忽视了呈现给单个细胞的凝胶局部量的异质性的重要性,导致
单细胞水平上可变且不明确的细胞-物质相互作用。我们在此描述了一种高效
独立于凝胶控制 3D 空间中单细胞周围微型水凝胶沉积的方法
成分和弹性。使用这种方法,我们的初步数据表明 MSC 的体积迅速扩大
当它们粘附在较薄的凝胶中的整合素配体上时。我们证明将单个 MSC 封装在薄凝胶中
即使凝胶弹性较低,涂层也足以增强 MSC 的成骨潜力。我们将建设
根据这些结果来检验控制单个 MSC 周围局部凝胶沉积影响的假设
通过调节细胞体积膨胀来实现膜张力和谱系规范。在目标 1 中,我们将确定
通过调节机械敏感离子,改变局部凝胶沉积对调节体积减少的影响
通道及其对 MSC 膜张力的影响。在目标 2 中,我们将确定局部凝胶的变化程度
沉积影响单个 MSC 的命运和基于 MSC 的骨再生。我们预测存在一个
当凝胶沉积变薄时选择性激活转录程序,从而
影响 MSC 谱系规格,与凝胶弹性无关。该项目是高度跨学科的
它将结合生物材料、生物物理、遗传和体内方法的专业知识
解决具体目标。结果将有助于将局部凝胶沉积定义为重要的决定因素
干细胞生长,从而影响干细胞力学和命运。鉴于这些细胞的临床相关性,
我们的结果将为基于 MSC 的疗法的配方设计提供信息,以改善再生结果。
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 }}
Jae-Won Shin其他文献
Jae-Won Shin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('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:
$ 40.02万 - 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:
$ 40.02万 - 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:
$ 40.02万 - 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:
$ 40.02万 - 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:
$ 40.02万 - 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:
$ 40.02万 - 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:
10598507 - 财政年份:2019
- 资助金额:
$ 40.02万 - 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:
$ 40.02万 - 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:
$ 40.02万 - 项目类别:
相似海外基金
Targeted ablation of cerebral atherosclerosis using supramolecular self-assembly
利用超分子自组装靶向消融脑动脉粥样硬化
- 批准号:
24K21101 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
心房細動に対するPulsed Field Ablationの組織創傷治癒過程を明らかにする網羅的研究
阐明房颤脉冲场消融组织伤口愈合过程的综合研究
- 批准号:
24K11201 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
遅延造影心臓MRIによる心房細動Ablation冷却効果の比較:28 vs. 31 mm Cryoballoon
使用延迟对比增强心脏 MRI 比较房颤消融冷却效果:28 毫米与 31 毫米 Cryoballoon
- 批准号:
24K11281 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
InSPACE-VT_Development and Validation of Virtual Pace Mapping to Guide Catheter Ablation of Ventricular Tachycardia
InSPACE-VT_虚拟起搏测绘的开发和验证以指导室性心动过速导管消融
- 批准号:
EP/Z001145/1 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Fellowship
CAREER: Heat Penetration Depth and Direction Control with Closed-Loop Device for Precision Ablation
职业:利用闭环装置控制热穿透深度和方向,实现精确烧蚀
- 批准号:
2338890 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
- 批准号:
2334777 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
- 批准号:
2334775 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
- 批准号:
2334776 - 财政年份:2024
- 资助金额:
$ 40.02万 - 项目类别:
Continuing Grant
Cryo laser-ablation system (157+193nm) with 'triple-quad' plasma mass spectrometer, Cryo-LA-ICPMS/MS
带有“三重四极杆”等离子体质谱仪、Cryo-LA-ICPMS/MS 的冷冻激光烧蚀系统 (157 193nm)
- 批准号:
515081333 - 财政年份:2023
- 资助金额:
$ 40.02万 - 项目类别:
Major Research Instrumentation
MRI: Acquisition of a Laser Ablation - Inductively Coupled Plasma - Triple Quadrupole - Mass Spectrometer (LA-ICP-QQQ-MS) System For Research and Education
MRI:获取用于研究和教育的激光烧蚀 - 电感耦合等离子体 - 三重四极杆 - 质谱仪 (LA-ICP-MS/MS) 系统
- 批准号:
2320040 - 财政年份:2023
- 资助金额:
$ 40.02万 - 项目类别:
Standard Grant