Toward Xeno-free Stem Cell Culture: Nanofiber-directed Differentiation of mESC to Neurons

迈向无异源干细胞培养:纳米纤维定向分化 mESC 至神经元

基本信息

  • 批准号:
    8812048
  • 负责人:
  • 金额:
    $ 37.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-01-01 至 2018-12-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION: The use of xenogenic, costly, and complicated culture media and substrates during stem cell expansion and differentiation procedures has greatly limited their widespread use and translational relevance. To address these barriers, we have developed a synthetic nanofiber substrate that induces differentiation of mouse embryonic stem cells to neural progenitors within 1 day. Our proposed nanofibers use combinations of topography, alignment, and the tethering of up to three individually bioactive peptides where the presentation and concentration can be controlled precisely to influence cell membrane signaling interactions. Therefore, this proposal seeks to develop this multi-peptide tethered culture substrate for the directed differentiation and maturation of neurons and glia. We are uniquely positioned to develop a synthetic culture substrate capable of providing multiple functionalization sites for directed mouse embryonic stem cell differentiation; no other group to date offers more than 1 tethered peptide functionalization site. In this R15 proposal, we will direct stem cell differentiation by (i) characterizing the impact of surface-tethered bioactive molecules on neural lineage commitment (glial or neuronal) differentiation and maturity, and (ii) directing differentiation of mESCs into neural lineages via controlled surface interaction rather than soluble factors. The outcomes of these two aims will provide a novel, synthetic culture substrate for differentiation and long-term culture of mature neural cells. These outcomes have broad implications, as these culture substrates could be further modified to control the differentiation and maturity of other lineages. The PIs have excellent track records with research training, with the majority of the undergraduate students trained in their laboratories advancing into research-based, health-related graduate programs. If funded, the proposed project would significantly enhance the research environment in two colleges at The University of Akron. Both PIs have actively integrated undergraduates into their research laboratories, resulting in 18 co-authored papers (including 5 first-authored papers) over the past 5 years.
 产品说明:在干细胞扩增和分化过程中使用异种的、昂贵的和复杂的培养基和底物极大地限制了它们的广泛使用和翻译相关性。为了解决这些障碍,我们已经开发了一种合成的神经干细胞底物,其在1天内诱导小鼠胚胎干细胞分化为神经祖细胞。我们提出的纳米纤维使用拓扑结构,对齐和拴系多达三个单独的生物活性肽的组合,其中可以精确控制呈递和浓度以影响细胞膜信号相互作用。因此,该提议寻求开发用于神经元和神经胶质的定向分化和成熟的这种多肽系留的培养基质。我们独特地定位于开发能够为定向小鼠胚胎干细胞分化提供多个功能化位点的合成培养基质;迄今为止,没有其他组提供超过1个拴系肽功能化位点。在这个R15提案中,我们将通过(i)表征表面束缚的生物活性分子对神经谱系定型(神经胶质或神经元)分化和成熟的影响,以及(ii)通过受控的表面相互作用而不是可溶性因子将mESC分化为神经谱系来指导干细胞分化。这两个目标的结果将为成熟神经细胞的分化和长期培养提供一种新的合成培养基质。这些结果具有广泛的意义,因为这些培养基质可以进一步修改,以控制其他谱系的分化和成熟。PI在研究培训方面有着出色的记录,大多数在实验室接受培训的本科生都进入了以研究为基础的健康相关研究生课程。如果获得资助,拟议的项目将大大提高在阿克伦大学的两个学院的研究环境。这两个PI都积极地将本科生融入他们的研究实验室,在过去的5年中,共发表了18篇合著论文(包括5篇第一作者论文)。

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mechanotransduction of Neural Cells Through Cell-Substrate Interactions.
通过细胞-基质相互作用进行神经细胞的机械转导。
  • DOI:
    10.1089/ten.teb.2015.0380
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Stukel,JessicaM;Willits,RebeccaKuntz
  • 通讯作者:
    Willits,RebeccaKuntz
Postfabrication Tethering of Molecular Gradients on Aligned Nanofibers of Functional Poly(ε-caprolactone)s.
  • DOI:
    10.1021/acs.biomac.9b01264
  • 发表时间:
    2019-12-09
  • 期刊:
  • 影响因子:
    6.2
  • 作者:
    Silantyeva EA;Willits RK;Becker ML
  • 通讯作者:
    Becker ML
Accelerated neural differentiation of mouse embryonic stem cells on aligned GYIGSR-functionalized nanofibers.
  • DOI:
    10.1016/j.actbio.2018.05.052
  • 发表时间:
    2018-07-15
  • 期刊:
  • 影响因子:
    9.7
  • 作者:
    Silantyeva EA;Nasir W;Carpenter J;Manahan O;Becker ML;Willits RK
  • 通讯作者:
    Willits RK
{{ 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 }}

Matthew L Becker其他文献

Rapid (<3 min) microwave synthesis of block copolymer templated ordered mesoporous metal oxide and carbonate films using nitrate-citric acid systems.
使用硝酸盐-柠檬酸系统快速(<3 分钟)微波合成嵌段共聚物模板有序介孔金属氧化物和碳酸盐膜。
  • DOI:
    10.1039/c4cc09808k
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    4.9
  • 作者:
    Yuanzhong Zhang;Sarang M. Bhaway;Yi Wang;Kevin A. Cavicchi;Matthew L Becker;Bryan D Vogt
  • 通讯作者:
    Bryan D Vogt

Matthew L Becker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('Matthew L Becker', 18)}}的其他基金

Synergistic Enhancement of Peripheral Nerve Defect Repair using Peptide Functionalized Aligned Nanofiber Conduits
使用肽功能化对齐纳米纤维导管协同增强周围神经缺损修复
  • 批准号:
    10786183
  • 财政年份:
    2022
  • 资助金额:
    $ 37.34万
  • 项目类别:
Synergistic Enhancement of Peripheral Nerve Defect Repair using Peptide Functionalized Aligned Nanofiber Conduits
使用肽功能化对齐纳米纤维导管协同增强周围神经缺损修复
  • 批准号:
    10626956
  • 财政年份:
    2022
  • 资助金额:
    $ 37.34万
  • 项目类别:

相似海外基金

The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
  • 批准号:
    EP/Z000920/1
  • 财政年份:
    2025
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
  • 批准号:
    FT230100276
  • 财政年份:
    2024
  • 资助金额:
    $ 37.34万
  • 项目类别:
    ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
  • 批准号:
    MR/X024261/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
  • 批准号:
    DE240100388
  • 财政年份:
    2024
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
  • 批准号:
    2889694
  • 财政年份:
    2023
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
  • 批准号:
    2842926
  • 财政年份:
    2023
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
  • 批准号:
    NC/X001644/1
  • 财政年份:
    2023
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
  • 批准号:
    2337595
  • 财政年份:
    2023
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
  • 批准号:
    2232190
  • 财政年份:
    2023
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
  • 批准号:
    23K17514
  • 财政年份:
    2023
  • 资助金额:
    $ 37.34万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了