TY - JOUR
T1 - Mesenchymal stem cell-mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice
AU - Yamaza, Takayoshi
AU - Miura, Yasuo
AU - Akiyama, Kentaro
AU - Bi, Yanming
AU - Sonoyama, Wataru
AU - Gronthos, Stan
AU - Chen, Wanjun
AU - Le, Anh
AU - Shi, Songtao
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2009/3/12
Y1 - 2009/3/12
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2008-10-182246
DO - 10.1182/blood-2008-10-182246
M3 - Article
C2 - 19074727
AN - SCOPUS:63849280638
VL - 113
SP - 2595
EP - 2604
JO - Blood
JF - Blood
SN - 0006-4971
IS - 11
ER -