Submitted October 2, 2008
Accepted December 7, 2008
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, and Songtao Shi*
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, United States
Graduate School of Medicine, Kyoto University, Kyoto, Japan
National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia
* Corresponding author; email: songtaos{at}usc.edu.
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 reported that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate (HA/TCP) as a carrier suppressed age-related degeneration in multi-organs and benefited an increase in lifespan extension as compared to control littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis via the erythropoietin receptor (EPO-R)/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 EPO-R/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age related degeneration of multi-organs in adult immunocompromised mice.
