GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATION

牙龈源性间充质干细胞:在免疫调节和组织再生中的作用

基本信息

  • 批准号:
    8271275
  • 负责人:
  • 金额:
    $ 1.76万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-06-01 至 2012-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT A major roadblock in regenerative medicine is the ability to resolve disease-associated inflammation and to optimize tissue regenerative capacity to prevent further tissue destruction secondary to inflammation or scarring. Recently, a major breakthrough in mesenchymal stem cells (MSCs) research identifies an intrinsic role of MSCs in immune-regulatory function. We have demonstrated that pro-inflammatory cytokines are required for immunosuppressive function of MSCs through the concerted action of chemokines, and nitric oxide, and that activated T cells can induce apoptosis of MSCs via the Fas/Fas L pathway. Our studies also have revealed that the immunosuppressive property of skin derived MSCs were tightly regulated by the local inflammatory niche mediated by the autocrine/paracrine IL17/IL6 axis, and therapeutic approaches targeting these distinct niche components resulted in suppression of excessive scar formation. Based on these observations, we explore the feasibility of isolating MSCs from human gingiva (hGMSCs), a unique oral tissue that functions both as a biological mucosal barrier and a component of the oral mucosal immunity. Interestingly, hGMSCs exhibit not only multipotent differentiation and self-renewal capacities but also possess superior immunosuppressive effect as compared to bone marrow mesenchymal stem cells (BMMSC), by inducing Tregs expansion and inhibiting Th17 cells, and consequently, suppress tissue destruction in our inflammation-related tissue injury/osteonecrosis model induced by bisphosphonate (BRONJ). We hypothesize that GMSCs are capable of playing dual roles in tissue repair including a protective role as an immunomodulator to inhibit tissue injury and a tissue regeneration role through their multipotent differentiation capacities. In this application, our interdisciplinary team with advanced specialties in stem cell biology, immunology, tissue repair/regeneration, and clinical therapies, proposes to elucidate the molecular mechanisms of inflammation- related tissue injury/degeneration, and develop a novel therapeutic approach using GMSCs to suppress inflammation and promote regeneration/reconstruction of diseased and injured oral and craniofacial tissues. Our objective will be addressed using three integrated specific aims: 1) To further delineate stem cell properties of hGMSCs at the single colony level; 2) To determine whether hGMSCs are capable of immunomodulation and the underlying mechanisms; and 3) To explore the feasibility of targeting GMSCs to reduce inflammation and promote tissue regeneration in animal models of inflammation- related oral disorders/diseases. This study will substantially extend current knowledge of the immunomodulatory functions of GMSCs and provide critical pre-clinical data to test the feasibility and efficacy of novel therapeutic approach using GMSC to harness inflammation and enhance regeneration of inflammation-related or injured orofacial tissues.
项目总结/文摘

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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Anh D Le其他文献

Oral soft tissue wound healing
口腔软组织伤口愈合

Anh D Le的其他文献

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{{ truncateString('Anh D Le', 18)}}的其他基金

Targeted inhibition of eIF5Ahpu suppresses tumor growth and M2-like TAM polarization in oral cancer
靶向抑制 eIF5Ahpu 可抑制口腔癌中的肿瘤生长和 M2 样 TAM 极化
  • 批准号:
    10573290
  • 财政年份:
    2022
  • 资助金额:
    $ 1.76万
  • 项目类别:
Targeted inhibition of eIF5Ahpu suppresses tumor growth and M2-like TAM polarization in oral cancer
靶向抑制 eIF5Ahpu 可抑制口腔癌中的肿瘤生长和 M2 样 TAM 极化
  • 批准号:
    10441837
  • 财政年份:
    2022
  • 资助金额:
    $ 1.76万
  • 项目类别:
Therapeutic Potential of Gingival mesenchymal Stem Cell-derived Extracellular Vesicles Enriched with MFG-E8 in Peripheral Nerve Regeneration
富含 MFG-E8 的牙龈间充质干细胞来源的细胞外囊泡在周围神经再生中的治疗潜力
  • 批准号:
    10180941
  • 财政年份:
    2020
  • 资助金额:
    $ 1.76万
  • 项目类别:
Therapeutic Potential of Gingival mesenchymal Stem Cell-derived Extracellular Vesicles Enriched with MFG-E8 in Peripheral Nerve Regeneration
富含 MFG-E8 的牙龈间充质干细胞来源的细胞外囊泡在周围神经再生中的治疗潜力
  • 批准号:
    10042927
  • 财政年份:
    2020
  • 资助金额:
    $ 1.76万
  • 项目类别:
GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATION
牙龈源性间充质干细胞:在免疫调节和组织再生中的作用
  • 批准号:
    7728606
  • 财政年份:
    2009
  • 资助金额:
    $ 1.76万
  • 项目类别:
GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATION
牙龈源性间充质干细胞:在免疫调节和组织再生中的作用
  • 批准号:
    7851425
  • 财政年份:
    2009
  • 资助金额:
    $ 1.76万
  • 项目类别:
GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATION
牙龈源性间充质干细胞:在免疫调节和组织再生中的作用
  • 批准号:
    8070529
  • 财政年份:
    2009
  • 资助金额:
    $ 1.76万
  • 项目类别:
GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATION
牙龈源性间充质干细胞:在免疫调节和组织再生中的作用
  • 批准号:
    8466720
  • 财政年份:
    2009
  • 资助金额:
    $ 1.76万
  • 项目类别:
GINGIVA DERIVED MSCS: ROLE IN IMMUNOMODULATION AND TISSUE REGENERATION
牙龈源性间充质干细胞:在免疫调节和组织再生中的作用
  • 批准号:
    8600475
  • 财政年份:
    2009
  • 资助金额:
    $ 1.76万
  • 项目类别:
BOWMAN-BIRK INHIBITOR CONCENTRATE & ORAL LEUKOPLAKIA: PHASE IIB TRIAL (UNIVER
BOWMAN-BIRK 抑制剂浓缩液
  • 批准号:
    7716696
  • 财政年份:
    2008
  • 资助金额:
    $ 1.76万
  • 项目类别:

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