Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
3-12-2009
Publication Source
Blood
Volume
113
Issue
11
Start Page
2595
Last Page
2604
DOI
10.1182/blood-2008-10-182246
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.
Keywords
EMTREE drug terms: calcium phosphate, 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
Recommended Citation
Yamaza, T., Miura, Y., Akiyama, K., Bi, Y., Sonoyama, W., Gronthos, S., Chen, W., Le, A., & Shi, S. (2009). Mesenchymal Stem Cell-Mediated Ectopic Hematopoiesis Alleviates Aging-Related Phenotype in Immunocompromised Mice. Blood, 113 (11), 2595-2604. http://dx.doi.org/10.1182/blood-2008-10-182246
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
At the time of publication, author Anh D. Le was affiliated with the Center for Craniofacial Molecular Biology, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Songtao Shi was affiliated with the Center for Craniofacial Molecular Biology, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.