Forced expression of human macrophage colony-stimulating factor in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro
(2017) In European Journal of Haematology- 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.
(Less)
- author
- Montano, Carmen
LU
; Thudium, Christian S.
LU
; Löfvall, Henrik
LU
; Moscatelli, Ilana LU ; Schambach, Axel ; Henriksen, Kim and Richter, Johan LU
- organization
- publishing date
- 2017-02-03
- 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 Haematology
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:28160330
- wos:000399882100012
- scopus:85014432762
- ISSN
- 0902-4441
- DOI
- 10.1111/ejh.12867
- project
- Improving our understanding of osteoclasts in bone metabolic diseases through novel osteoclast models
- language
- English
- LU publication?
- yes
- id
- 22fdaf53-29b6-4b8c-8120-632a7c347cb5
- date added to LUP
- 2017-03-24 15:25:55
- date last changed
- 2025-01-07 10:19:03
@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}}, keywords = {{Cord blood CD34 cells; Human M-CSF; Lentiviral transduction; Monocytes; Osteoclast; Transplantation}}, language = {{eng}}, month = {{02}}, publisher = {{Wiley-Blackwell}}, series = {{European Journal of Haematology}}, 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}}, doi = {{10.1111/ejh.12867}}, year = {{2017}}, }