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

Date

2009

Authors

Yamaza, T.
Miura, Y.
Akiyama, K.
Bi, Y.
Sonoyama, W.
Gronthos, S.
Chen, W.
Le, A.
Shi, S.

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Journal article

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Blood, 2009; 113(11):2595-2604

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

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Abstract

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 littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis 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 phenotypes and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice.

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Copyright © 2009 by American Society of Hematology

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