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Direct and indirect contributions of perivascular stem cells to bone healing

Direct and indirect contributions of perivascular stem cells to bone healing
血管周围干细胞对骨愈合的直接和间接贡献
批准号:
10203809
负责人:
AARON W JAMES
金额:
$27.59万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-08-28 至 2023-06-30

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中文摘要
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英文摘要
PROJECT SUMMARY As an alternative to autograft bone, mesenchymal stem cells (MSC) have been employed to accelerate bone repair. However, current MSC sources have significant drawbacks, including: (1) scarce availability, (2) need for culture, and (3) significant cell heterogeneity with decreased bone-forming efficacy. Our solution is the use of a novel, purified and uncultured stem cell source, known as Perivascular Stem Cells (PSC). PSC are prospectively purified ancestors of culture-derived, traditional MSC, and are identified by their presence around vessels. Unlike bone marrow stem cells (BMSC), PSC have significant advantages for clinical translation, including: (1) isolation by fluorescence activated cell sorting (FACS) rather than culture, (2) high homogeneity, and (3) high quantity for clinical application. Our data show that PSC exert bone healing effects via both direct and paracrine mechanisms, including a combination of pro-osteogenic and pro-vasculogenic effects on host bone tissue. Exciting recent data suggest that PSC frequency, viability, growth and differentiation factor (GDF) elaboration and osteogenic differentiation are resistant to the detrimental effects of osteoporotic bone loss. In contrast, BMSC show reduced numbers, proliferation, and osteogenic differentiation potential with osteoporosis. This marked difference has led us to directly and systematically compare the bone healing potential of PSC versus BMSC in the current proposal. Overall, the following Early Stage / New Investigator application will address the cellular and signaling mechanisms through which perivascular stem cells promote bone healing through direct and indirect effects, and their unique resistance to osteoporotic conditions. AIM 1: Evaluate the direct and paracrine effects of PSC in bone healing. Through a systematic series of studies, we will examine the effects of PSC on osteoprogenitor cell migration and differentiation, as well as angiogenesis and neovascularization in bone healing. Osteoblast and endothelial cell reporter animals will be utilized to compare host:donor cell contributions in our previously described femoral segmental defect (FSD) model. Studies will be performed head-to-head with culture-derived BMSC application. Differences in bone healing outcomes between treatment groups will be statistically correlated with in vitro GDF elaboration. AIM 2: Demonstrate the importance of host versus donor osteoporosis in PSC bone healing. As mentioned, PSC demonstrate marked resistance to the detrimental effects of osteoporotic bone loss. However, our pilot data suggest that osteoporotic status of the ‘host bone’ but not ‘donor MSC’ may impact bone healing. Here, we will determine the extent to which osteoporosis within transplanted PSC or host bone tissue affects bone healing. Studies will be performed head-to-head with culture-derived BMSC application in our FSD model. Differences in bone healing will be correlated with GDF and bone inhibitory signal expression.
期刊论文(42)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1016/j.jor.2019.02.015
发表时间: 2019-05
期刊: Journal of orthopaedics
影响因子: 1.5
作者: [Takashi Sono;C. Meyers;Daniel Miller;Catherine Ding;E. McCarthy;A. James]
通讯作者: Takashi Sono;C. Meyers;Daniel Miller;Catherine Ding;E. McCarthy;A. James
Pharmacological inhibition of DKK1 promotes spine fusion in an ovariectomized rat model.
DKK1 的药理学抑制可促进卵巢切除大鼠模型中的脊柱融合。
DOI: 10.1016/j.bone.2022.116456
发表时间: 2022
期刊: Bone
影响因子: 4.1
作者: [Li,Zhao, Xing,Xin, Gomez-Salazar,MarioArmando, Xu,Mingxin, Negri,Stefano, Xu,Jiajia, James,AaronW]
通讯作者: James,AaronW
Pericytes for Therapeutic Bone Repair.
用于治疗性骨修复的周细胞。
DOI: 10.1007/978-3-030-02601-1_3
发表时间: 2018
期刊: Advances in experimental medicine and biology
影响因子: --
作者: [Meyers,CarolynA, Casamitjana,Joan, Chang,Leslie, Zhang,Lei, James,AaronW, Péault,Bruno]
通讯作者: Péault,Bruno
DOI: 10.1093/stcltm/szad024
发表时间: 2023-07-14
期刊: Stem cells translational medicine
影响因子: 6
作者: []
通讯作者:
22
    Biostimulatory nanofiber-hydrogel composite for soft tissue remodeling
    • 批准号:
      10391846
    • 项目类别:
    • 资助金额:
      $56.86万
    • 财政年份:
      2022
    • 负责人:
      AARON W JAMES
    • 依托单位:
    Biostimulatory nanofiber-hydrogel composite for soft tissue remodeling
    • 批准号:
      10551877
    • 项目类别:
    • 资助金额:
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    • 财政年份:
      2022
    • 负责人:
      AARON W JAMES
    • 依托单位:
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    • 批准号:
      10685946
    • 项目类别:
    • 资助金额:
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    • 财政年份:
      2022
    • 负责人:
      AARON W JAMES
    • 依托单位:
    Defining the human adventitial stem cell niche
    • 批准号:
      10386241
    • 项目类别:
    • 资助金额:
      $22.64万
    • 财政年份:
      2022
    • 负责人:
      AARON W JAMES
    • 依托单位:
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