Forced expression of human macrophage colony-stimulating factor in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro.
Eur J Haematol
; 98(5): 517-526, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28160330
ABSTRACT
OBJECTIVES:
Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (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 were 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Monócitos
/
Expressão Gênica
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Diferenciação Celular
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Fator Estimulador de Colônias de Macrófagos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Haematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Suécia