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Adaptive changes of adipose tissue to hypoxia : cell death-mediated activation of stem cells

Research Project

Project/Area Number 22659320
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Plastic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

YOSHIMURA Kotaro  東京大学, 医学部附属病院, 講師 (60210762)

Co-Investigator(Kenkyū-buntansha) HIGASHINO Takuya  東京大学, 医学部附属病院, 助教 (70433901)
荒木 淳  東京大学, 医学部附属病院, 特任臨床医 (00508088)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,190,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords脂肪由来幹細胞 / 血管内皮細胞 / 虚血 / 創傷治癒 / 血管新生 / 細胞死因子
Research Abstract

Based on the analysis of exudates from injured adipose tissue, we prepared a mixture containing the injury-associated growth factors at the same proportion as the exudates, named adipose injury cocktail(AIC). We hypothesized that AIC induces a series of regenerating and angiogenic processes without actual wounding. The purpose of this study is to elucidate therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor cells(ASCs) to proliferate, migrate, and form capillary networks compared to vascular endothelial cells, while VEGF did not induce mitogenesis or chemotaxis in hASCs. Each component growth factor of AIC was differently responsible for the ASC activation. AIC-treated ASCs tended to differentiate into adipocytes or vessel-constituting cells rather than other cell types. In ischemic adipose tissues of mice, induced either by a surgical intervention or by diabetes, AIC administration enhanced proliferation, especially of CD31-/CD34+ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggested that AIC may have therapeutic potentials for various ischemic/hypoxic conditions by inducing adipose remodeling and neovascularization through activation of ASCs and other cells. Treatment with AIC has many advantages over cell-based therapies with regard to morbidity, cost, and physical risks, and may be used for an alternative therapy for improving tissue oxygen tension.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (4 results)

All 2012 2011 2010

All Journal Article (4 results) (of which Peer Reviewed: 4 results)

  • [Journal Article] The fate of adipocytes after non-vascularized fat grafting : Evidence of early death and replacement of adipocytes2012

    • Author(s)
      Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S, Yoshimura K
    • Journal Title

      Plast Reconstr Surg

      Volume: 129 Pages: 1081-1092

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adipose injury-associated factors mitigate hypoxia in ischemic tissues through activation of adipose stem/stromal cells and induction angiogenesis2012

    • Author(s)
      Eto H, et al.
    • Journal Title

      American Journal of Pathology

      Volume: 178 Pages: 2322-2332

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adipose injury-associated factors mitigate hypoxia in ischemic tissues through activation of adipose stem/stromal cells and induction angiogenesis2011

    • Author(s)
      Eto H, Suga H, Aoi N, Kato H, Araki J, Doi K, Higashino T, Yoshimura K
    • Journal Title

      Am J Pathol

      Volume: 178 Pages: 2322-2332

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adipose tissue remodeling under ischemia : Death of adipocytes and activation of stem/progenitor cells.2010

    • Author(s)
      Suga H, Eto H, Aoi N, Kato H, Araki J, Doi K, Yoshimura K.
    • Journal Title

      Plast Reconstr Surg

      Volume: 126 Pages: 1911-1923

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed

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Published: 2010-08-23   Modified: 2016-04-21  

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