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

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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; Thudium, Christian S.; Löfvall, Henrik; Moscatelli, Ilana; Schambach, Axel; Henriksen, Kim; Richter, Johan.

In: European Journal of Haematology, 03.02.2017.

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T1 - Forced expression of human macrophage colony-stimulating factor in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro

AU - Montano, Carmen

AU - Thudium, Christian S.

AU - Löfvall, Henrik

AU - Moscatelli, Ilana

AU - Schambach, Axel

AU - Henriksen, Kim

AU - Richter, Johan

PY - 2017/2/3

Y1 - 2017/2/3

N2 - 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.

AB - 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.

KW - Cord blood CD34 cells

KW - Human M-CSF

KW - Lentiviral transduction

KW - Monocytes

KW - Osteoclast

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=85014432762&partnerID=8YFLogxK

U2 - 10.1111/ejh.12867

DO - 10.1111/ejh.12867

M3 - Article

JO - European Journal of Haematology

T2 - European Journal of Haematology

JF - European Journal of Haematology

SN - 1600-0609

ER -