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Human CD34+ progenitor cells freshly isolated from umbilical cord blood attenuate inflammatory lung injury following LPS challenge.

Huang X, Sun K, Zhao YD, Vogel SM, Song Y, Mahmud N, Zhao YY - PLoS ONE (2014)

Bottom Line: We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability.In contrast, CD34(-) cells had no effects on lung vascular injury.Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Department of Pharmacology, School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.

ABSTRACT
Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34(+) progenitor cells (fCB-CD34(+) cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34(+) cells were transplanted i.v. to mice while CD34(-) cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34(-) cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34(+) cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34(-) cell-treated controls. Importantly, lung inflammation in fCB-CD34(+) cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34(-) cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34(+) cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34(+) cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34(+) cells are an important source of stem cells for the treatment of acute lung injury.

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fCB-CD34+ cell treatment-induced endothelial cell proliferation in lungs.(A) Representative micrographs of immunofluorescent staining. Lung tissues were collected at 52 h post-LPS challenge, sectioned and immunostained with anti-BrdU (green) and anti-vWF/CD31 (red) antibodies. Nuclei were counterstained with DAPI (blue). Arrows indicate proliferating EC. Scale bar: 50 µm. (B) Quantification of BrdU-positive EC (vWF+ and/or CD31002B) and non-EC (vWF− and/or CD31−). Data are expressed as mean ± SD (n = 4/group). *, P<0.001 versus PBS or CD34−.
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pone-0088814-g006: fCB-CD34+ cell treatment-induced endothelial cell proliferation in lungs.(A) Representative micrographs of immunofluorescent staining. Lung tissues were collected at 52 h post-LPS challenge, sectioned and immunostained with anti-BrdU (green) and anti-vWF/CD31 (red) antibodies. Nuclei were counterstained with DAPI (blue). Arrows indicate proliferating EC. Scale bar: 50 µm. (B) Quantification of BrdU-positive EC (vWF+ and/or CD31002B) and non-EC (vWF− and/or CD31−). Data are expressed as mean ± SD (n = 4/group). *, P<0.001 versus PBS or CD34−.

Mentions: To determine whether fCB-CD34+ cell treatment induces endothelial cell proliferation thereby promotes vascular repair [31], we assessed cell proliferation by in vivo BrdU labeling. Quantification of BrdU-positive EC (expressing either CD31 mainly in large vessels or vWF in capillaries) revealed that fCB-CD34+ cell treatment induced a marked increase of EC proliferation in mouse lungs at 52 h post-LPS challenge which was approximately 4-fold greater than PBS-treated controls. EC proliferation in lungs of mice treated with CD34− was similar to PBS-treated controls (Fig. 6).


Human CD34+ progenitor cells freshly isolated from umbilical cord blood attenuate inflammatory lung injury following LPS challenge.

Huang X, Sun K, Zhao YD, Vogel SM, Song Y, Mahmud N, Zhao YY - PLoS ONE (2014)

fCB-CD34+ cell treatment-induced endothelial cell proliferation in lungs.(A) Representative micrographs of immunofluorescent staining. Lung tissues were collected at 52 h post-LPS challenge, sectioned and immunostained with anti-BrdU (green) and anti-vWF/CD31 (red) antibodies. Nuclei were counterstained with DAPI (blue). Arrows indicate proliferating EC. Scale bar: 50 µm. (B) Quantification of BrdU-positive EC (vWF+ and/or CD31002B) and non-EC (vWF− and/or CD31−). Data are expressed as mean ± SD (n = 4/group). *, P<0.001 versus PBS or CD34−.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928308&req=5

pone-0088814-g006: fCB-CD34+ cell treatment-induced endothelial cell proliferation in lungs.(A) Representative micrographs of immunofluorescent staining. Lung tissues were collected at 52 h post-LPS challenge, sectioned and immunostained with anti-BrdU (green) and anti-vWF/CD31 (red) antibodies. Nuclei were counterstained with DAPI (blue). Arrows indicate proliferating EC. Scale bar: 50 µm. (B) Quantification of BrdU-positive EC (vWF+ and/or CD31002B) and non-EC (vWF− and/or CD31−). Data are expressed as mean ± SD (n = 4/group). *, P<0.001 versus PBS or CD34−.
Mentions: To determine whether fCB-CD34+ cell treatment induces endothelial cell proliferation thereby promotes vascular repair [31], we assessed cell proliferation by in vivo BrdU labeling. Quantification of BrdU-positive EC (expressing either CD31 mainly in large vessels or vWF in capillaries) revealed that fCB-CD34+ cell treatment induced a marked increase of EC proliferation in mouse lungs at 52 h post-LPS challenge which was approximately 4-fold greater than PBS-treated controls. EC proliferation in lungs of mice treated with CD34− was similar to PBS-treated controls (Fig. 6).

Bottom Line: We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability.In contrast, CD34(-) cells had no effects on lung vascular injury.Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America ; Department of Pharmacology, School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.

ABSTRACT
Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34(+) progenitor cells (fCB-CD34(+) cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34(+) cells were transplanted i.v. to mice while CD34(-) cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34(-) cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34(+) cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34(-) cell-treated controls. Importantly, lung inflammation in fCB-CD34(+) cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34(-) cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34(+) cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34(+) cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34(+) cells are an important source of stem cells for the treatment of acute lung injury.

Show MeSH
Related in: MedlinePlus