Bone marrow mesenchymal stem cell transplantation suppresses emphysema-induced inflammation and apoptosis

doi:10.3969/j.issn.2095-4344.2014.06.014

Abstract

Abstract:

BACKGROUND: Bone marrow mesenchymal stem cells transplantation can change the surrounding microenvironment through paracrine mechanisms, and can be employed for treatment of serious damage to lung function through the promotion of angiogenesis, inhibition of apoptosis and maintaining functional stability of autonomic nervous system.

OBJECTIVE: To observe the inflammatory reaction in experimental emphysema and inhibition of apoptosis through bone marrow mesenchymal stem cells transplantation.

METHODS: Twenty-four Wistar female rats were randomly divided into three groups: healthy control group, model group and experimental group. In the latter two groups, smoking and endotracheal instillation of porcine pancreatic elastase were performed to establish emphysema models. After modeling, bone marrow mesenchymal stem cells were injected via tail vein in the experimental group. Pathological changes of the lung, the level of tumor necrosis factor-alpha and cell number in the bronchoalveolar lavage fluid as well as apoptotic index in lveolar walls were detected after cell transplantation.

RESULTS AND CONCLUSION: In the model and experimental groups, pathological changes of lung tissues were observed to different extent. The lung pathological changes were slighter in the experimental group than the model group (P < 0.01). The level of tumor necrosis factor-alpha and apoptotic index in lung tissue were lower in the experimental group than the model group (P < 0.01). These findings indicate that bone marrow mesenchymal stem cells can improve emphysema pathologically through inhibition of inflammatory response and apoptosis in experimental emphysema.

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

全文链接：

Key words: stem cells, mesenchymal stem cells, bone marrow, cell transplantation, pulmonary emphysema, bronchoalveolar lavage fluid

CLC Number:

R394.2

Zhao Xiao-jian, Lu Cai-ping, Chu Wei-wei, Zhen Qiang, Tan Guo-liang, Zhang Ya-xiao, Wang Ren-feng, Zhang Bing, Liu Jia-bao. Bone marrow mesenchymal stem cell transplantation suppresses emphysema-induced inflammation and apoptosis[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(6): 906-911.

Figures/Tables 2

2.1 实验动物数量分析实验共纳入大鼠总数为25只，其中1只取骨髓细胞，其他入组大鼠均进行造模，造模成功率100%，所有大鼠均进入结果分析。 2.2 培养的骨髓间充质干细胞形态及鉴定细胞悬液中为骨髓间充质干细胞呈圆形，悬浮状态。24 h出现贴壁细胞，72 h贴壁细胞多呈三角形、多角形或梭形，胞体饱满，胞浆半透明，细胞核呈圆形，核仁明显，常向外伸出2-4个长短不同的突起。培养到7 d时胞体增大，细胞形状逐渐以梭形为主，相互之间连接更加紧密。传代后的细胞生长速度比原代细胞快，细胞密度增大，汇流处的骨髓间充质干细胞形态较均一，为长梭形，呈旋涡状或平行生长，光性较强。10-14 d时细胞80%融合，细胞呈平行排列生长或漩涡状生长。流式细胞仪检测CD44(84.69%)，CD90(90.54%)，CD71(70.32%)，CD45(2.87%)[10]。 2.3 大鼠支气管肺泡灌洗液中细胞总数和细胞分类计数与健康对照组比较，模型组大鼠支气管肺泡灌洗液中细胞总数，中性粒细胞、淋巴细胞百分比明显升高(P < 0.01)；与模型组比较，实验组大鼠支气管肺泡灌洗液中细胞总数明显降低(P < 0.01)，细胞分类计数差异无显著性意义(表1)。 2.4 大鼠肺组织形态学观察及测定模型组及实验组均呈现呼吸性细支气管、肺泡管、肺泡等不同程度扩大，肺泡大小不一，肺泡数目明显减少，肺泡间隔变薄，部分间隔断裂致肺泡融合等肺气肿样改变，但实验组较模型组为轻。模型组和实验组平均内衬间隔及平均肺泡数明显高于健康对照组(P < 0.01)，平均肺泡数明显低于健康对照组(P < 0.01)。而模型组平均内衬间隔及平均肺泡数明显高于实验组(P < 0.01)，平均肺泡数明显低于实验组(P < 0.01，图1和表2)。"

References

[1] Zhao Y, Cui A, Wang F, et al. Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema. Chin Med J (Engl). 2012;125(17):3015-3021.

[2] Tanabe N, Muro S, Tanaka S, et al. Emphysema distribution and annual changes in pulmonary function in male patients with chronic obstructive pulmonary disease.Respir Res. 2012; 13:31.

[3] Thébaud B, Ladha F, Michelakis ED, et al. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia- induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation. 2005;112(16): 2477-2486.

[4] 孙琰玮,李宝平,王轩,等.Ad-GFP修饰的间充质干细胞在肺气肿大鼠体内向肺部的定向迁移[J].中国组织工程研究与临床康复, 2010,14(14):2528-2532.

[5] 戈霞晖,白冲.间充质干细胞与肺疾病的研究进展[J].国际呼吸杂志,2010,20(17):1069-1071.

[6] Li BP, Zhao XJ, Song YM, et al. Restoration of pathological changes of emphysema by angiogenesis factors: experiment of rats. Zhonghua Yi Xue Za Zhi. 2007;87(33):2365-2368.

[7] 李宝平,赵晓建,宋永明,等.骨髓间充质干细胞移植对实验性肺气肿大鼠动脉血气及肺组织病理学变化的影响(英文)[J].中国组织工程研究与临床康复,2007,11(50):10176-10180.

[8] Cyranoski D. Stem cells in Texas: Cowboy culture. Nature. 2013;494(7436):166-168.

[9] Vincent LG, Engler AJ. Stem cell differentiation: Post-degradation forces kick in. Nat Mater. 2013;12(5): 384-386.

[10] Jacobs SA,Roobrouck VD,Verfaillie CM,et al. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Immunol Cell Biol. 2013; 91(1):32-39.

[11] Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome: a review. Chest. 2012;141(1):222- 231.

[12] Vidal D, Fortunato G, Klein W, et al. Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances. Rev Port Pneumol. 2012;18(3):128-136.

[13] Tzouvelekis A, Zacharis G, Oikonomou A, et al. Combined pulmonary fibrosis and emphysema associated with microscopic polyangiitis. Eur Respir J. 2012;40(2):505-507.

[14] Tanabe N, Muro S, Sato S, et al. Longitudinal study of spatially heterogeneous emphysema progression in current smokers with chronic obstructive pulmonary disease. PLoS One. 2012;7(9):e44993.

[15] Adir Y, Shachner R, Amir O, et al. Severe pulmonary hypertension associated with emphysema: a new phenotype. Chest. 2012;142(6):1654-1658.

[16] Le PF, Das NJC, Cazes A, et al. Lung volume reduction surgery for emphysema and bullous pulmonary emphysema. Rev Pneumol Clin. 2012;68(2):131-145.

[17] Arango E, Espinosa D, Illana J, et al. Lung volume reduction surgery after lung transplantation for emphysema-chronic obstructive pulmonary disease. Transplant Proc. 2012;44(7): 2115-2117.

[18] Roulet A, Armand L,Dagouassat M,et al. Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats. BMC Pulm Med. 2012;12:38.

[19] Kishaba T, Shimaoka Y, Fukuyama H, et al. A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema. BMJ Open. 2012;2(3). pii: e000988.

[20] Caramori G, Casolari P, Garofano E, et al. Role of stem cells in the pathogenesis of chronic obstructive pulmonary disease and of pulmonary emphysema]. Recenti Prog Med. 2012; 103(1):31-40.

[21] Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013 Jul 23.

[22] Longhini-Dos-Santos N, Barbosa-de-Oliveira VA, Kozma RH, et al. Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema. Stem Cell Rev. 2013;9(2):210-218. Stem Cell Rev. 2013;9(2):210-218.

[23] Lau AN, Goodwin M, Kim CF, et al. Stem cells and regenerative medicine in lung biology and diseases. Mol Ther. 2012;20(6):1116-1130.

[24] 李宝平,邢万红,路鹏雁,等.生长因子及骨髓间充质干细胞与肺再血管化修复烟熏大鼠肺气肿模型[J].中国组织工程研究与临床康复,2010,14(2):227-232.

[25] 邹健勇,罗红鹤,陈振光.骨髓间充质干细胞在特发性肺纤维化治疗中的潜在应用价值[J].中国组织工程研究与临床康复,2008, 12(47):9339-9342.

[26] Ma S, Zhong D, Chen H, et al. The immunomodulatory effect of bone marrow stromal cells (BMSCs) on interleukin (IL)-23/IL-17-mediated ischemic stroke in mice. J Neuroimmunol. 2013;257(1-2):28-35.

[27] Song G, Habibovic P, Bao C, et al. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate. Biomaterials. 2013;34(9):2167-2176.

[28] Tian Z, Li Y, Ji P, et al. Mesenchymal stem cells protects hyperoxia-induced lung injury in newborn rats via inhibiting receptor for advanced glycation end-products/nuclear factor kappaB signaling. Exp Biol Med (Maywood). 2013;238(2): 242-247.

[29] Andreeva ER, Buravkova LB. Multipotent mesenchymal stromal and immune cells interaction: reciprocal effects. Ross Fiziol Zh Im I M Sechenova. 2012;98(12):1441-1459.

[30] Casiraghi F, Perico N, Remuzzi G. Mesenchymal stromal cells to promote solid organ transplantation tolerance. Curr Opin Organ Transplant. 2013;18(1):51-58.