Continuous root formation in developing teeth by molecular cues

通过分子线索在牙齿发育过程中持续形成牙根

基本信息

  • 批准号:
    9237255
  • 负责人:
  • 金额:
    $ 72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-04-01 至 2021-03-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Dental caries and pulpitis cause developmental arrest of tooth roots of permanent teeth in children and adolescents. Wide-open root apex is susceptible to trauma and infections, frequently resulting in tooth loss at a young age (typically <18 years old). Tooth loss in children and adolescent patients is devastating because titanium dental implants are contra-indicated due to metal submerge in the alveolar bone that undergoes active vertical growth. Currently, there is no effective clinical treatment for infected permanent teeth with open root apex in children and adolescent patients. Regenerative cells or cues that promote dentin formation and continuous root development offer the only hope to address this unmet clinical need. Craniofacial mesenchymal stem/progenitor cells in development differentiate into odontoblasts that form dentin. Our preliminary data show that a panel of 948 genes and transcriptional factors are up- or down-regulated when craniofacial mesenchymal stem/progenitor cells differentiate into odontoblasts. We delivered two rationally selected factors in endodontically treated root canals in a preclinical model in vivo and found robust dentin regeneration in the form of tubular dentin with dentinal tubules and odontoblast processes as demonstrated by electron microscopy. Mechanical properties of the regenerated dentin were at par with native dentin that served as a substrate for the newly formed, regenerated dentin. Strikingly, no cells were transplanted in endodontically treated root canals. Thus, all of the regenerated dentin was derived from host endogenous cells that were recruited by these two molecular cues. In this application, we transform our newly gained knowledge on endogenous dentin regeneration in mature teeth into immature teeth with wide-open root apex in a preclinical, large animal model that is equivalent to developing permanent teeth in children and adolescent patients. This translation from mature teeth to immature teeth is far from a simple chronological switch, but will address two scientifically unknown and clinically relevant questions: 1) Can single molecular cues not only induce the recruitment of sufficient endogenous apical papilla stem/progenitor cells, but also transform them into dentin-generating odontoblasts? 2) Can spatiotemporal delivery of molecular cues promote directional dentin growth to complete root development? Accordingly, the overall objectives of this proposal, in response to PAR-13-137 (Bioengineering Research Grants, BRG), are to develop novel strategies for dentin regeneration in immature teeth with wide open root apex in a preclinical, large animal model. Our overarching hypothesis is that dentin regeneration in immature teeth with wide-open root apex is enabled by signal gradients of novel molecular cues that induce the recruitment and differentiation of endogenous stem/progenitor cells.


项目成果

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JEREMY J MAO其他文献

JEREMY J MAO的其他文献

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{{ truncateString('JEREMY J MAO', 18)}}的其他基金

Pre-clinical Models of Odontic Analogs by Endogenous Stem Cells
内源干细胞的牙类似物的临床前模型
  • 批准号:
    8421709
  • 财政年份:
    2013
  • 资助金额:
    $ 72万
  • 项目类别:
Multidisciplinary Training in TMJ Disorders/Pain: Integrating Basic, Translation
颞下颌关节疾病/疼痛的多学科培训:整合基础、翻译
  • 批准号:
    8568459
  • 财政年份:
    2013
  • 资助金额:
    $ 72万
  • 项目类别:
Multidisciplinary Training in TMJ Disorders/Pain: Integrating Basic, Translation
颞下颌关节疾病/疼痛的多学科培训:整合基础、翻译
  • 批准号:
    8691782
  • 财政年份:
    2013
  • 资助金额:
    $ 72万
  • 项目类别:
Multidisciplinary Training in TMJ Disorders/Pain: Integrating Basic, Translation
颞下颌关节疾病/疼痛的多学科培训:整合基础、翻译
  • 批准号:
    8900124
  • 财政年份:
    2013
  • 资助金额:
    $ 72万
  • 项目类别:
Pre-clinical Models of Odontic Analogs by Endogenous Stem Cells
内源干细胞的牙类似物的临床前模型
  • 批准号:
    8901766
  • 财政年份:
    2013
  • 资助金额:
    $ 72万
  • 项目类别:
International Conference on Dental and Craniofacial Stem Cells
国际牙科和颅面干细胞会议
  • 批准号:
    8007279
  • 财政年份:
    2011
  • 资助金额:
    $ 72万
  • 项目类别:
Regeneration of Clinically Relevant Orofacial Tissues in Pre-Clinical Models
临床前模型中临床相关口面部组织的再生
  • 批准号:
    7939746
  • 财政年份:
    2009
  • 资助金额:
    $ 72万
  • 项目类别:
Engineering of Vascularized Bone
血管化骨工程
  • 批准号:
    8308943
  • 财政年份:
    2009
  • 资助金额:
    $ 72万
  • 项目类别:
Tracking stem cells in engineered tissue and organs in vivo and in real time
体内实时追踪工程组织和器官中的干细胞
  • 批准号:
    8319267
  • 财政年份:
    2009
  • 资助金额:
    $ 72万
  • 项目类别:
Tracking stem cells in engineered tissue and organs in vivo and in real time
体内实时追踪工程组织和器官中的干细胞
  • 批准号:
    7691514
  • 财政年份:
    2009
  • 资助金额:
    $ 72万
  • 项目类别:

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