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

Montano, Carmen LU ; Thudium, Christian S. LU ; Löfvall, Henrik LU ; Moscatelli, Ilana LU ; Schambach, Axel; Henriksen, Kim and Richter, Johan LU (2017) In European Journal of Haematology1987-01-01+01:00
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... (More)

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.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Cord blood CD34 cells, Human M-CSF, Lentiviral transduction, Monocytes, Osteoclast, Transplantation
in
European Journal of Haematology1987-01-01+01:00
publisher
Wiley-Blackwell
external identifiers
  • scopus:85014432762
  • wos:000399882100012
ISSN
0902-4441
DOI
10.1111/ejh.12867
language
English
LU publication?
yes
id
22fdaf53-29b6-4b8c-8120-632a7c347cb5
date added to LUP
2017-03-24 15:25:55
date last changed
2018-01-07 11:56:59
@article{22fdaf53-29b6-4b8c-8120-632a7c347cb5,
  abstract     = {<p>Objectives: Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34<sup>+</sup> 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<sup>+</sup> cells using a lentiviral vector. Results: We show that LV-hM-CSF-transduced CB CD34<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> cells receiving exogenous hM-CSF. NSG mice engrafted with LV-hM-CSF-transduced CB CD34<sup>+</sup> 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<sup>+</sup> 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.</p>},
  author       = {Montano, Carmen and Thudium, Christian S. and Löfvall, Henrik and Moscatelli, Ilana and Schambach, Axel and Henriksen, Kim and Richter, Johan},
  issn         = {0902-4441},
  keyword      = {Cord blood CD34 cells,Human M-CSF,Lentiviral transduction,Monocytes,Osteoclast,Transplantation},
  language     = {eng},
  month        = {02},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Haematology1987-01-01+01:00},
  title        = {Forced expression of human macrophage colony-stimulating factor in CD34<sup>+</sup> cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro},
  url          = {http://dx.doi.org/10.1111/ejh.12867},
  year         = {2017},
}