Mesenchymal Stem Cell-Mediated Ectopic Hematopoiesis Alleviates Aging-Related Phenotype in Immunocompromised Mice
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erythropoietin receptor
hydroxyapatite
Klotho protein
somatomedin C
STAT5 protein EMTREE medical terms: aging
animal cell
animal model
article
bone marrow cell
cellular immunity
comparative study
controlled study
degeneration
female
hematopoiesis
hematopoietic stem cell transplantation
human
human cell
immune deficiency
lifespan
mesenchymal stem cell
mouse
nonhuman
nucleotide sequence
phenotype
priority journal
recipient
regulatory mechanism
Dentistry
Oral Biology and Oral Pathology
Periodontics and Periodontology
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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 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. © 2009 by The American Society of Hematology.