Forced expression of human macrophage colony-stimulating factor in CD34+cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro

Autor: Axel Schambach, Ilana Moscatelli, Kim Henriksen, Johan Richter, Carmen P. Montano Almendras, Christian S. Thudium, Henrik Löfvall
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Haematology. 98:517-526
ISSN: 0902-4441
Popis: Objectives Here we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in CB CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo. Methods Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vector. Results We show that LV-hM-CSF-transduced CB CD34+ cells expand 3.6 and 8.5 fold more with one or two exposures to the hM-CSF expressing vector, respectively, when compared to control cells. Likewise, LV-hM-CSF-transduced CB CD34+cells show significantly higher levels of monocytes. In addition, these cells produced high levels of hM-CSF. Furthermore, they are able to differentiate into functional bone resorbing osteoclasts in vitro. However, osteoclast differentiation and bone resorption was blunted compared to control CD34+ cells receiving exogenous hM-CSF. NSG mice engrafted with LV-hM-CSF-transduced CB CD34+ cells have physiological levels of hM-CSF production that result in an increase in the percentage of human monocytes in peripheral blood and bone marrow as well as in the spleen, lung and liver. Conclusion In summary, ectopic production of human M-CSF in CD34+ cells promotes cellular expansion and monocyte differentiation in vitro and in vivo and allows for the formation of functional osteoclasts, albeit at reduced levels, without an exogenous source of M-CSF, in vitro. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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