Mesenchymal stem cell-mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice

Takayoshi Yamaza, Yasuo Miura, Kentaro Akiyama, Yanming Bi, Wataru Sonoyama, Stan Gronthos, Wanjun Chen, Anh Le, Songtao Shi

研究成果: ジャーナルへの寄稿学術論文査読

40 被引用数 (Scopus)

抄録

Subcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age- related degeneration in multiple organs and benefited an increase in life span extension compared with control litter- mates. The newly organized ectopic bone/ marrow system restores active hemato-poiesis via the erythropoietin receptor/ signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like pheno-types and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hema-topoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice.

本文言語英語
ページ(範囲)2595-2604
ページ数10
ジャーナルBlood
113
11
DOI
出版ステータス出版済み - 12-03-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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