Experimental studyOther graftTherapeutic Effects of Bone Marrow-Derived Mesenchymal Stem Cells Engraftment on Bleomycin-Induced Lung Injury in Rats
Section snippets
Animals
Adult Sprague-Dawley rats (200–250 g body weight) were obtained from our laboratory animal center. Animals were kept in accordance with the National Institutes of Health Guidelines on the Use of Laboratory Animals. All animals used in this study were of the same genetic background. The experimental protocols were approved by the Fourth Military Medical University Committee on Animal Care.
Preparing for Bone Marrow-Derived MSCs
MSCs were isolated from rat bone marrow. In brief, whole marrow was flushed from the tibia and femur of
Histopathologic Analysis
Rat lung histologic sections from each experimental group are shown in Figs 1 A–H. There was no obvious lesion in the lung of normal control rats. In the lung injury group, HE staining showed the pulmonary alveolus cavity to obviously be decreased in size, the alveolar wall thickened, mesenchyme expanded with increased numbers of fibroblasts and macrophages. In Masson stains collagen, was increased in the lung interstitium as well as around blood vessels and bronchi when compared with normal
Discussion
Our studies showed that MSCs differentiated into alveolar epithelial cells in BLM-induced injury of rat lung. The decreased HYP, LN, and HA confirmed that MSC engraftment attenuated lung injury and fibrosis. We believe that the amelioration was associated with the decrease in TGF-β1, PDGF-A, PDGF-B, and IGF-I in injured rat lungs.
The technique of cell labeling in this study was important to identify differentiating cells derived from donor animals. The fluorescent dye DAPI selectively binds to
References (23)
- et al.
Human mesenchymal stem cells modulate allogeneic immune cell responses
Blood
(2005) - et al.
The role of transforming growth factor β in lung development and disease
Chest
(2004) - et al.
IL-4 upregulates tenascin synthesis in scleroderma and healthy skin fibroblasts
J Invest Dermato
(1996) - et al.
Idiopathic pulmonary fibrosis: current and future treatment options
Am J Respir Med
(2002) Idiopathic pulmonary fibrosis: diagnosis and treatmentInternational consensus statement
Am J Respir Crit Care Med
(2000)Marrow stromal cells as stem cells for nonhematopoietic tissues
Science
(1997)- et al.
Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects
Proc Natl Acad Sci
(2003) - et al.
Bone marrow-derived mesenchymal stem cells in repair of the injured lung
Am J Respir Cell Mol Biol
(2005) - et al.
TGF-beta1 stimulation of cell locomotion utilizes the hyaluronan receptor RHAMM and hyaluronan
J Cell Biol
(1993) - et al.
Irradiation-induced expression of hyaluronan (HA) synthase 2 and hyaluronidase 2 genes in rat lung tissue accompanies active turnover of HA and induction of types I and III collagen gene expression
Am J Respir Cell Mol Biol
(2000)