Mesenchymal stem cell-mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice.
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.
Yamaza
Takayoshi
T
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.
Miura
Yasuo
Y
Akiyama
Kentaro
K
Bi
Yanming
Y
Sonoyama
Wataru
W
Gronthos
Stan
S
Chen
Wanjun
W
Le
Anh
A
Shi
Songtao
S
D000375:Aging / Q000276:immunology / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology / Q000502:physiology*; D008017:Life Expectancy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008822:Mice, Transgenic; D010641:Phenotype; D012038:Regeneration / Q000502:physiology
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins