Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb;37(2):133-9.
doi: 10.14348/molcells.2014.2317. Epub 2014 Feb 19.

Therapeutic use of stem cell transplantation for cell replacement or cytoprotective effect of microvesicle released from mesenchymal stem cell

Moonhwan Choi  1 , Taehyun Ban, Taiyoun Rhim
Affiliations

Therapeutic use of stem cell transplantation for cell replacement or cytoprotective effect of microvesicle released from mesenchymal stem cell

Moonhwan Choi et al. Mol Cells. 2014 Feb.

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treatment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Schematic representation of silica induced pulmonary fibrosis model with hMSC or MV treatment. The SiO2-induced IPF mice model was treated with hMSC or MV. IT, intratracheal; IV, intravein treated.
Fig. 2.
Fig. 2.
The effect MSC or MV treatment on lung wet/dry ratio with silica induced pulmonary fibrosis in mice. Female C57BL/6J mice were randomly divided into four groups with five mice in each group: control, pulmonary fibrosis, hMSC treated and MV treated group. (A) Weight of left upper lobe of the lung. (B) The wet-to-dry ratio of left upper lung lobe (*p < 0.05).
Fig. 3.
Fig. 3.
The inflammatory cell distribution in BAL fluid of pulmonary fibrosis model mice with hMSC or MV treatment. BAL fluids were collected and analyzed for the numbers of macrophages (A), neutrophils (B) and lymphocytes (C). The number of neutrophils, lymphocytes, and macrophages in the BAL fluid increased in pulmonary fibrosis model and treatment of hMSCs or MV reduced the number of inflammatory cells in BAL fluid. Treatment of hMSCs or MV decrease the percentage of foamy macrophages among total alveolar macrophages (D).
Fig. 4.
Fig. 4.
Diff-quick staining of BAL cells. Numbers of total BAL cells were increased in silica induced fibrosis model (B), however treatment of hMSC or MV driven hMSC significantly decreased the BAL cells in the airway (C, D). Foamy macrophages were indicated with arrow head.
Fig. 5.
Fig. 5.
Effect of hMSCs or microvesicle transfer on collagen deposition in lung tissues. Collagen deposition in the lungs was analyzed using Masson’s Trichrome stain (B). Stained areas were quantified using NIH Image J software (http://rsb.info.nih.gov/ij/). (C) *p < 0.05 compared with the fibrosis group.
Fig. 6.
Fig. 6.
Collagen I and SMA-α expression following hMSCs or MV treatment. Concentrations of type I collagen and Smooth muscle actin-α were measured by Western blot analysis (A) followed by densitometric quantification (B).
Fig. 7.
Fig. 7.
The Detection of functionally differentiated hMSCs in mouse lung. Representative images of H&E staining immunofluorescent staining for human-specific nuclear antigen (HuNu, green) (A). Detection of lung-specific human sftpb (surfactant protein B) expression by RT-PCR (B). Amplified cDNA sequence was determined and compared with mouse (NM_001282071) and human SFTPB (NM_000542) cDNA sequences.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akao Y., Iio A., Itoh T., Noguchi S., Itoh Y., Ohtsuki Y., Naoe T. Microvesicle-mediated RNA molecule delivery system using monocytes/macrophages. Mol. Ther. 2011;19:395–399. - PMC - PubMed
    1. Banerjee E.R., Laflamme M.A., Papayannopoulou T., Kahn M., Murry C.E., Henderson W.R., Jr Human embryonic stem cells differentiated to lung lineage-specific cells ameliorate pulmonary fibrosis in a xenograft transplant mouse model. PLoS One. 2012;7:e33165. - PMC - PubMed
    1. Bedrossian C., Warren C., Ohar J., Jackson F. Amiodarone pulmonary toxicity - cytopathology ultrastructure and immunocytochemistry. Lab. Invest. 1991;64:A113–A113. - PubMed
    1. Camussi G., Deregibus M.C., Bruno S., Cantaluppi V., Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 2010;78:838–848. - PubMed
    1. Guttentag S.H., Beers M.F., Bieler B.M., Ballard P.L. Surfactant protein B processing in human fetal lung. Am. J. Physiol. 1998;275:L559–566. - PubMed

Publication types

MeSH terms

Substances