Bone marrow mesenchymal stem cells with reduced glutathione against mouse lung injury

doi:10.3969/j.issn.2095-4344.2015.23.004

Abstract

Abstract:

BACKGROUND: A large number of experiments have shown that bone marrow mesenchymal stem cells (BMSCs) have good effects on the treatment of lung disease or improvement of lung injury, and its therapeutic effect is mainly oriented to reduce the inflammatory response.
OBJECTIVE: To study the effects of BMSCs combined with reduced glutathione in murine models of bleomycin-induced lung injury.
METHODS: BMSCs were isolated from a male NOD/SCID mouse and cell morphology and phenotype were
observed. Sixty-four female NOD/SCID mice were randomly divided into a control group, a model group, a BMSCs group and a BMSCs+reduced glutathione group (combined group). The control group received intratracheal injection of normal saline, the model group received intratracheal injection of bleomycin, and the BMSC group received BMSCs injection via the tail vein at 2 hours after intratracheal injection of bleomycin, and combined group received BMSCs+reduced glutathione injection via the tail vein at 2 hours after intratracheal injection of bleomycin. All mice were killed after 7 days, and levels of tumor necrosis factor-α, interleukin-β, malondialdehyde in lung tissue were detected and lung tissue specimens were obtained for pathological examination.
RESULTS AND CONCLUSION: BMSCs were fibroblast-like cells, Positive for CD10, CD13 and CD44, but negative for CD34 and CD45. Compared with the control group, the levels of tumor necrosis factor-α, interleukin-β and malondialdehyde were increased in the model group, while decreased significantly in the BMSCs group and combined group (P < 0.05), especially in the combined group (P < 0.05). Pathological examination showed that more serious lung injury was observed in the model group and BMSCs group than the combined group. These findings indicate that BMSCs combined with reduced glutathione can more effectively protect against bleomycin-induced lung injury.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mesenchymal Stem Cells, Glutathione;, Lung Injury

CLC Number:

R394.2

Chen Fei, Li Guo-qing, Hu Feng-qing, Mei Ju, Wang Ming-song. Bone marrow mesenchymal stem cells with reduced glutathione against mouse lung injury [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(23): 3628-3632.

Figures/Tables 3

References

[1] Tsoutsou PG, Koukourakis MI. Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research. Int J Radiat Oncol Biol Phys. 2006;66(5):1281-1293.

[2] Chen Y, Williams J, Ding I, et al. Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol. 2002; 12(1 Suppl 1):26-33.

[3] Krause DS, Theise ND, Collector MI, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001;105(3):369-377.

[4] Kotton DN, Ma BY, Cardoso WV, et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development. 2001;128(24):5181-5188.

[5] 王莉,方妮,张伟京,等.骨实质来源间质干细胞对博莱霉素诱导小鼠肺损伤的保护作用[J].解放军医学杂志,2008,33(10): 1220-1224.

[6] Dillioglugil MO, Ilgazli A, Maral H, et al. Protective effects of N-acetylcysteine on the peroxidative changes of rat lungs exposed to inhalation of thinners. Respirology. 2005;10(5):615-619.

[7] Ritter C, da Cunha AA, Echer IC, et al. Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide- induced acute lung injury in the rat. Crit Care Med. 2006;34(2): 471-477.

[8] Usuki J, Matsuda K, Azuma A, et al. Sequential analysis of myofibroblast differentiation and transforming growth factor-β1/Smad pathway activation in murine pulmonary fibrosis. J Nippon Med Sch. 2012;79(1):46-59.

[9] Zhao F, Zhang YF, Liu YG, et al. Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplant Proc. 2008; 40(5):1700-1705.

[10] Shi Y, Su J, Roberts AI, et al. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 2012; 33(3):136-143.

[11] Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005;33(2):145-152.

[12] Aslam M, Baveja R, Liang OD, et al. Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med. 2009; 180(11): 1122-1130.

[13] Gomez-de-Antonio D, Zurita M, Santos M, et al. Stem cells and bronchial stump healing. J Thorac Cardiovasc Surg. 2010; 140(6):1397-1401.

[14] Wang L, Tu XH, Zhao P, et al. Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats. Mol Med Rep. 2012; 6(2):287-292.

[15] 康新勤,藏伟进,宋土生,等.大鼠骨髓间充质干细胞分离培养及其形态观察[J].西安交通大学学报:医学版,2003,24(5):518-519.

[16] Haddad JJ, Olver RE, Land SC. Antioxidant/pro-oxidant equilibrium regulates HIF-1alpha and NF-kappa B redox sensitivity. Evidence for inhibition by glutathione oxidation in alveolar epithelial cells. J Biol Chem. 2000;275(28):21130- 21139.

[17] Slater AF, Stefan C, Nobel I, et al. Signalling mechanisms and oxidative stress in apoptosis. Toxicol Lett. 1995;82-83: 149-153.

[18] 金婧,董淑红,苏力,等.新生大鼠内毒素性急性肺损伤肺组织 MDA、SOD和IL-10、IL-18的改变[J].新生儿科杂志, 2004,19(2): 69-72.