衰老与肺纤维化和慢性阻塞性肺疾病以及间充质干细胞的治疗作用
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摘要
背景:衰老与肺纤维化、慢性阻塞性肺疾病的发生发展密切相关,间充质干细胞可能对衰老相关的肺纤维化和慢性阻塞性肺疾病有治疗作用。目的:综述衰老与肺纤维化和慢性阻塞性肺疾病的关系以及间充质干细胞对其治疗的效果和机制。方法:检索PubMed数据库、CNKI数据库中2005年6月至2018年10月关于肺纤维化、慢性阻塞性肺疾病与衰老的关系以及间充质干细胞治疗慢性阻塞性肺疾病和肺纤维化的文章,中文检索词为"肺纤维化,慢性阻塞性肺疾病,衰老,间充质干细胞",英文检索词为"pulmonary fibrosis,COPD,aging,MSCs",排除陈旧性和无关研究,最后选择64篇文献进行综述。结果与结论:端粒长度调节、细胞和免疫衰老、氧化应激以及许多抗衰老分子和细胞外基质的变化等与肺纤维化、慢性阻塞性肺疾病密切相关。间充质干细胞作为一种具有自我更新、多向分化和分泌活性的多功能细胞,能从抗氧化应激、调节衰老分子、减少细胞衰老与凋亡等多个衰老关键表型的角度出发,治疗与衰老有关的肺纤维化和慢性阻塞性肺疾病。
BACKGROUND: Aging is closely related to the occurrence and development of pulmonary fibrosis and chronic obstructive pulmonary disease, and mesenchymal stem cells may have therapeutic effects on senile pulmonary fibrosis and chronic obstructive pulmonary disease due to their characteristics. OBJECTIVE: To review the relationship between aging and pulmonary fibrosis and chronic obstructive pulmonary disease, as well as the therapeutic effect and mechanism of mesenchymal stem cells. METHODS: PubMed and CNKI database were searched for articles published from June 2005 to October 2018 on pulmonary fibrosis, the relationship between chronic obstructive pulmonary disease and aging, as well as the relationship between mesenchymal stem cells for the treatment of chronic obstructive pulmonary disease and pulmonary fibrosis. The key words in Chinese were "pulmonary fibrosis, chronic obstructive pulmonary disease, aging, mesenchymal stem cells", and the English terms were "pulmonary fibrosis, COPD, aging, MSCs." Obsolete and unrelated studies were excluded, and finally 64 articles were reviewed. RESULTS AND CONCLUSION: Length of the telomere, cell and immunosenescence, oxidative stress and many anti-aging molecules and changes in the extracellular matrix are closely related to pulmonary fibrosis and chronic obstructive pulmonary disease. Mesenchymal stem cells are pluripotent cells that have self-renewal, multilineage differentiation and secretion activity, adjust the aging molecules from oxidation stress, and reduce cell senescence and apoptosis, to treat pulmonary fibrosis associated with aging and chronic obstructive pulmonary disease.
BACKGROUND: Aging is closely related to the occurrence and development of pulmonary fibrosis and chronic obstructive pulmonary disease, and mesenchymal stem cells may have therapeutic effects on senile pulmonary fibrosis and chronic obstructive pulmonary disease due to their characteristics. OBJECTIVE: To review the relationship between aging and pulmonary fibrosis and chronic obstructive pulmonary disease, as well as the therapeutic effect and mechanism of mesenchymal stem cells. METHODS: PubMed and CNKI database were searched for articles published from June 2005 to October 2018 on pulmonary fibrosis, the relationship between chronic obstructive pulmonary disease and aging, as well as the relationship between mesenchymal stem cells for the treatment of chronic obstructive pulmonary disease and pulmonary fibrosis. The key words in Chinese were "pulmonary fibrosis, chronic obstructive pulmonary disease, aging, mesenchymal stem cells", and the English terms were "pulmonary fibrosis, COPD, aging, MSCs." Obsolete and unrelated studies were excluded, and finally 64 articles were reviewed. RESULTS AND CONCLUSION: Length of the telomere, cell and immunosenescence, oxidative stress and many anti-aging molecules and changes in the extracellular matrix are closely related to pulmonary fibrosis and chronic obstructive pulmonary disease. Mesenchymal stem cells are pluripotent cells that have self-renewal, multilineage differentiation and secretion activity, adjust the aging molecules from oxidation stress, and reduce cell senescence and apoptosis, to treat pulmonary fibrosis associated with aging and chronic obstructive pulmonary disease.
引文
[1]陈艳玫,刘子锋,李贤德,等.2015-2050年中国人口老龄化趋势与老年人口预测[J].中国社会医学杂志,2018,35(5):480-483.
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[4]Sgalla G,Iovene B,Calvello M,et al.Idiopathic pulmonary fibrosis:pathogenesis and management.Respir Res.2018;19(1):32.
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[7]Tran D,Rajwani K,Berlin DA.Pulmonary effects of aging.Curr Opin Anaesthesiol.2018;31(1):19-23.
[8]Braman SS,Skloot GS.Pulmonary Disease in the Aging Patient.Clin Geriatr Med.2017;33(4):xi-xii.
[9]Guarente L.Sirtuins,aging,and metabolism.Cold Spring Harb Symp Quant Biol.2011;76:81-90.
[10]Ascher K,Elliot SJ,Rubio GA,et al.Lung Diseases of the Elderly:Cellular Mechanisms.Clin Geriatr Med.2017;33(4):473-490.
[11]Xu J,Gonzalez ET,Iyer SS,et al.Use of senescenceaccelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice.J Gerontol A Biol Sci Med Sci.2009;64(7):731-739.
[12]Vidacek N?,Nanic L,Ravlic S,et al.Telomeres,Nutrition,and Longevity:Can We Really Navigate Our Aging.J Gerontol A Biol Sci Med Sci.2017;73(1):39-47.
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[14]Müller KC,Welker L,Paasch K,et al.Lung fibroblasts from patients with emphysema show markers of senescence in vitro.Respir Res.2006;7:32.
[15]Armanios MY,Chen JJ,Cogan JD,et al.Telomerase mutations in families with idiopathic pulmonary fibrosis.N Engl J Med.2007;56(13):1317-1326.
[16]Tsakiri KD,Cronkhite JT,Kuan PJ,et al.Adult-onset pulmonary fibrosis caused by mutations in telomerase.Proc Natl Acad Sci US A.2007;104(18):7552-7557.
[17]Lawson WE,Loyd JE,Degryse AL.Genetics in pulmonary fibrosisfamilial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis.Am J Med Sci.2011;341(6):439-443.
[18]Harman D.Free radical theory of aging:an update:increasing the functional life span Ann N Y Acad Sci.2006;1067:10-21.
[19]MacNee W,Tuder RM.New paradigms in the pathogenesis of chronic obstructive pulmonary disease I.Proc Am Thorac Soc.2009;6(6):527-531.
[20]Malli F,Bardaka F,Tsilioni I,et al.8-isoprostane levels in serum and bronchoalveolar lavage in idiopathic pulmonary fibrosis and sarcoidosis.Food Chem Toxicol.2013;61:160-163.
[21]Burton DG,Krizhanovsky V.Physiological and pathological consequences of cellular senescence.Cell Mol Life Sci.2014;71(22):4373-4386.
[22]Tuder RM,Yoshida T,Fijalkowka I,et al.Role of lung maintenance program in the heterogeneity of lung destruction in emphysema.Proc Am Thorac Soc.2006;3(8):673-679.
[23]von Kobbe C.Cellular senescence:a view throughout organismal life.Cell Mol Life Sci.2018;75(19):3553-3567.
[24]Tsuji T,Aoshiba K,Nagai A.Alveolar cell senescence in patients with pulmonary emphysema.Am J Respir Crit Care Med.2006;174(8):886-893.
[25]Hecker L,Logsdon NJ,Kurundkar D,et al.Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance.Sci Transl Med.2014;6(231):231ra47.
[26]Minagawa S,Araya J,Numata T,et al.Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells.Am J Physiol Lung Cell Mol Physiol.2011;300(3):L391-401.
[27]Bustos ML,Huleihel L,Kapetanaki MG,et al.Aging mesenchymal stem cells fail to protect because of impaired migration and antiinflammatory response.Am J Respir Crit Care Med.2014;189(7):787-798.
[28]Dakhlallah D,Batte K,Wang Y,et al.Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis.Am J Respir Crit Care Med.2013;187(4):397-405.
[29]Ito K,Ito M,Elliott WM,et al.Decreased histone deacetylase activity in chronic obstructive pulmonary disease.N Engl J Med.2005;352(19):1967-1976.
[30]Baker JR,Vuppusetty C,Colley T,et al.Oxidative stress dependent microRNA-34a activation via PI3Kαreduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells.Sci Rep.2016;6:35871.
[31]Nikolich-Zugich J.The twilight of immunity:emerging concepts in aging of the immune system.Nat Immunol.2018;19(1):10-19.
[32]John-Schuster G,Günter S,Hager K,et al.Inflammaging increases susceptibility to cigarette smoke-induced COPD.Oncotarget.2016;7(21):30068-30083.
[33]Li L,Wang Y,Gao W,et al.Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease.J Biol Chem.2015;290(46):27890-27900.
[34]Gao W,Yuan C,Zhang J,et al.Klotho expression is reduced in COPD airway epithelial cells:effects on inflammation and oxidant injury.Clin Sci(Lond).2015;129(12):1011-1023.
[35]Acosta JC,Banito A,Wuestefeld T,et al.A complex secretory program orchestrated by the inflammasome controls paracrine senescence.Nat Cell Biol.2013;15(8):978-990.
[36]Brandsma CA,de Vries M,Costa R,et al.Lung ageing and COPD:is there a role for ageing in abnormal tissue repair.Eur Respir Rev.2017;26(146):170073.
[37]Hsu AC,Dua K,Starkey MR,et al.MicroRNA-125a and-b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD.JCI Insight.2017;2(7):e90443.
[38]Thannickal VJ,Henke CA,Horowitz JC,et al.Matrix biology of idiopathic pulmonary fibrosis:a workshop report of the national heart,lung,and blood institute.Am J Pathol.2014;184(6):1643-1651.
[39]Booth AJ,Hadley R,Cornett AM,et al.Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation.Am J Respir Crit Care Med.2012;186(9):866-876.
[40]Burgess JK,Mauad T,Tjin G,et al.The extracellular matrix-the under-recognized element in lung disease.J Pathol.2016;240(4):397-409.
[41]Lederer DJ,Martinez FJ.Idiopathic Pulmonary Fibrosis.N Engl JMed.2018;378(19):1811-1823.
[42]Jouneau S,Kerjouan M,Ricordel C.Danazol Treatment for Telomere Diseases.N Engl J Med.2016;375(11):1095.
[43]Brooks RW,Robbins PD.Treating Age-Related Diseases with Somatic Stem Cells.Adv Exp Med Biol.2018;1056:29-45.
[44]Liu YY,Chiang CH,Hung SC,et al.Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusioninduced lung injury.PLoS One.2017;12(11):e0187637.
[45]Johnson F,Giulivi C.Superoxide dismutases and their impact upon human health.Mol Aspects Med.2005;26(4-5):340-352.
[46]Huang K,Kang X,Wang X,et al.Conversion of bone marrow mesenchymal stem cells into type II alveolar epithelial cells reduces pulmonary fibrosis by decreasing oxidative stress in rats.Mol Med Rep.2015;11(3):1685-1692.
[47]Fredenburgh LE,Perrella MA,Mitsialis SA.The role of heme oxygenase-1 in pulmonary disease.Am J Respir Cell Mol Biol.2007;36(2):158-165.
[48]Liu G,Lv H,An Y,et al.Tracking of transplanted human umbilical cord-derived mesenchymal stem cells labeled with fluorescent probe in a mouse model of acute lung injury.Int J Mol Med.2018;41(5):2527-2534.
[49]Gazdhar A,Susuri N,Hostettler K,et al.HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic.PLoS One.2013;8(6):e65453.
[50]Tuder RM,Yun JH.Vascular endothelial growth factor of the lung:friend or foe.Curr Opin Pharmacol.2008;8(3):255-260.
[51]Guan XJ,Song L,Han FF,et al.Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors.J Cell Biochem.2013;114(2):323-335.
[52]Chen YB,Lan YW,Hung TH,et al.Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model.Cell Stress Chaperones.2015;20(4):643-652.
[53]Liu S,Liu D,Chen C,et al.MSC Transplantation Improves Osteopenia via Epigenetic Regulation of Notch Signaling in Lupus.Cell Metab.2015;22(4):606-618.
[54]Yuan Y,Shi M,Li L,et al.Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1αpathway.Clin Sci(Lond).2016;130(23):2181-2198.
[55]和法莲.人脐带间充质干细胞对小鼠老年性器官功能退变的治疗作用及其机制研究[D].昆明:昆明医科大学,2017.
[56]Vizoso FJ,Eiro N,Cid S,et al.Mesenchymal Stem Cell Secretome:Toward Cell-Free Therapeutic Strategies in Regenerative Medicine.Int J Mol Sci.2017;18(9):E1852.
[57]Gupta N,Su X,Popov B,et al.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice.JImmunol.2007;179(3):1855-1863.
[58]Li X,Wang Y,An G,et al.Bone marrow mesenchymal stem cells attenuate silica-induced pulmonary fibrosis via paracrine mechanisms.Toxicol Lett.2017;270:96-107.
[59]Liu HM,Liu YT,Zhang J,et al.Bone marrow mesenchymal stem cells ameliorate lung injury through anti-inflammatory and antibacterial effect in COPD mice.J Huazhong Univ Sci Technolog Med Sci.2017;37(4):496-504.
[60]Gu W,Song L,Li XM,et al.Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPKpathways.Sci Rep.2015;5:8733.
[61]Jackson MV,Morrison TJ,Doherty DF,et al.Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS.Stem Cells.2016;34(8):2210-2223.
[62]Moodley Y,Atienza D,Manuelpillai U,et al.Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury.Am J Pathol.2009;175(1):303-313.
[63]Fikry EM,Safar MM,Hasan WA,et al.Bone Marrow and AdiposeDerived Mesenchymal Stem Cells Alleviate Methotrexate-Induced Pulmonary Fibrosis in Rat:Comparison with Dexamethasone.JBiochem Mol Toxicol.2015;29(7):321-329.
[64]Jin Z,Pan X,Zhou K,et al.Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease.J Int Med Res.2015;43(3):303-310.
[2]Childs BG,Durik M,Baker DJ,et al.Cellular senescence in aging and age-related disease:from mechanisms to therapy.Nat Med.2015;21(12):1424-1435.
[3]Shioya T,Sato S,Iwakura M,et al.Improvement of physical activity in chronic obstructive pulmonary disease by pulmonary rehabilitation and pharmacological treatment.Respir Investig.2018;56(4):292-306.
[4]Sgalla G,Iovene B,Calvello M,et al.Idiopathic pulmonary fibrosis:pathogenesis and management.Respir Res.2018;19(1):32.
[5]Xi J,Yan X,Zhou J,et al.Mesenchymal stem cells in tissue repairing and regeneration:Progress and future.Burns Trauma.2013;1(1):13-20.
[6]Kirkwood TB.Understanding the odd science of aging.Cell.2005;120(4):437-447.
[7]Tran D,Rajwani K,Berlin DA.Pulmonary effects of aging.Curr Opin Anaesthesiol.2018;31(1):19-23.
[8]Braman SS,Skloot GS.Pulmonary Disease in the Aging Patient.Clin Geriatr Med.2017;33(4):xi-xii.
[9]Guarente L.Sirtuins,aging,and metabolism.Cold Spring Harb Symp Quant Biol.2011;76:81-90.
[10]Ascher K,Elliot SJ,Rubio GA,et al.Lung Diseases of the Elderly:Cellular Mechanisms.Clin Geriatr Med.2017;33(4):473-490.
[11]Xu J,Gonzalez ET,Iyer SS,et al.Use of senescenceaccelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice.J Gerontol A Biol Sci Med Sci.2009;64(7):731-739.
[12]Vidacek N?,Nanic L,Ravlic S,et al.Telomeres,Nutrition,and Longevity:Can We Really Navigate Our Aging.J Gerontol A Biol Sci Med Sci.2017;73(1):39-47.
[13]MorláM,Busquets X,Pons J,et al.Telomere shortening in smokers with and without COPD.Eur Respir J.2006;27(3):525-528.
[14]Müller KC,Welker L,Paasch K,et al.Lung fibroblasts from patients with emphysema show markers of senescence in vitro.Respir Res.2006;7:32.
[15]Armanios MY,Chen JJ,Cogan JD,et al.Telomerase mutations in families with idiopathic pulmonary fibrosis.N Engl J Med.2007;56(13):1317-1326.
[16]Tsakiri KD,Cronkhite JT,Kuan PJ,et al.Adult-onset pulmonary fibrosis caused by mutations in telomerase.Proc Natl Acad Sci US A.2007;104(18):7552-7557.
[17]Lawson WE,Loyd JE,Degryse AL.Genetics in pulmonary fibrosisfamilial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis.Am J Med Sci.2011;341(6):439-443.
[18]Harman D.Free radical theory of aging:an update:increasing the functional life span Ann N Y Acad Sci.2006;1067:10-21.
[19]MacNee W,Tuder RM.New paradigms in the pathogenesis of chronic obstructive pulmonary disease I.Proc Am Thorac Soc.2009;6(6):527-531.
[20]Malli F,Bardaka F,Tsilioni I,et al.8-isoprostane levels in serum and bronchoalveolar lavage in idiopathic pulmonary fibrosis and sarcoidosis.Food Chem Toxicol.2013;61:160-163.
[21]Burton DG,Krizhanovsky V.Physiological and pathological consequences of cellular senescence.Cell Mol Life Sci.2014;71(22):4373-4386.
[22]Tuder RM,Yoshida T,Fijalkowka I,et al.Role of lung maintenance program in the heterogeneity of lung destruction in emphysema.Proc Am Thorac Soc.2006;3(8):673-679.
[23]von Kobbe C.Cellular senescence:a view throughout organismal life.Cell Mol Life Sci.2018;75(19):3553-3567.
[24]Tsuji T,Aoshiba K,Nagai A.Alveolar cell senescence in patients with pulmonary emphysema.Am J Respir Crit Care Med.2006;174(8):886-893.
[25]Hecker L,Logsdon NJ,Kurundkar D,et al.Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance.Sci Transl Med.2014;6(231):231ra47.
[26]Minagawa S,Araya J,Numata T,et al.Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells.Am J Physiol Lung Cell Mol Physiol.2011;300(3):L391-401.
[27]Bustos ML,Huleihel L,Kapetanaki MG,et al.Aging mesenchymal stem cells fail to protect because of impaired migration and antiinflammatory response.Am J Respir Crit Care Med.2014;189(7):787-798.
[28]Dakhlallah D,Batte K,Wang Y,et al.Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis.Am J Respir Crit Care Med.2013;187(4):397-405.
[29]Ito K,Ito M,Elliott WM,et al.Decreased histone deacetylase activity in chronic obstructive pulmonary disease.N Engl J Med.2005;352(19):1967-1976.
[30]Baker JR,Vuppusetty C,Colley T,et al.Oxidative stress dependent microRNA-34a activation via PI3Kαreduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells.Sci Rep.2016;6:35871.
[31]Nikolich-Zugich J.The twilight of immunity:emerging concepts in aging of the immune system.Nat Immunol.2018;19(1):10-19.
[32]John-Schuster G,Günter S,Hager K,et al.Inflammaging increases susceptibility to cigarette smoke-induced COPD.Oncotarget.2016;7(21):30068-30083.
[33]Li L,Wang Y,Gao W,et al.Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease.J Biol Chem.2015;290(46):27890-27900.
[34]Gao W,Yuan C,Zhang J,et al.Klotho expression is reduced in COPD airway epithelial cells:effects on inflammation and oxidant injury.Clin Sci(Lond).2015;129(12):1011-1023.
[35]Acosta JC,Banito A,Wuestefeld T,et al.A complex secretory program orchestrated by the inflammasome controls paracrine senescence.Nat Cell Biol.2013;15(8):978-990.
[36]Brandsma CA,de Vries M,Costa R,et al.Lung ageing and COPD:is there a role for ageing in abnormal tissue repair.Eur Respir Rev.2017;26(146):170073.
[37]Hsu AC,Dua K,Starkey MR,et al.MicroRNA-125a and-b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD.JCI Insight.2017;2(7):e90443.
[38]Thannickal VJ,Henke CA,Horowitz JC,et al.Matrix biology of idiopathic pulmonary fibrosis:a workshop report of the national heart,lung,and blood institute.Am J Pathol.2014;184(6):1643-1651.
[39]Booth AJ,Hadley R,Cornett AM,et al.Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation.Am J Respir Crit Care Med.2012;186(9):866-876.
[40]Burgess JK,Mauad T,Tjin G,et al.The extracellular matrix-the under-recognized element in lung disease.J Pathol.2016;240(4):397-409.
[41]Lederer DJ,Martinez FJ.Idiopathic Pulmonary Fibrosis.N Engl JMed.2018;378(19):1811-1823.
[42]Jouneau S,Kerjouan M,Ricordel C.Danazol Treatment for Telomere Diseases.N Engl J Med.2016;375(11):1095.
[43]Brooks RW,Robbins PD.Treating Age-Related Diseases with Somatic Stem Cells.Adv Exp Med Biol.2018;1056:29-45.
[44]Liu YY,Chiang CH,Hung SC,et al.Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusioninduced lung injury.PLoS One.2017;12(11):e0187637.
[45]Johnson F,Giulivi C.Superoxide dismutases and their impact upon human health.Mol Aspects Med.2005;26(4-5):340-352.
[46]Huang K,Kang X,Wang X,et al.Conversion of bone marrow mesenchymal stem cells into type II alveolar epithelial cells reduces pulmonary fibrosis by decreasing oxidative stress in rats.Mol Med Rep.2015;11(3):1685-1692.
[47]Fredenburgh LE,Perrella MA,Mitsialis SA.The role of heme oxygenase-1 in pulmonary disease.Am J Respir Cell Mol Biol.2007;36(2):158-165.
[48]Liu G,Lv H,An Y,et al.Tracking of transplanted human umbilical cord-derived mesenchymal stem cells labeled with fluorescent probe in a mouse model of acute lung injury.Int J Mol Med.2018;41(5):2527-2534.
[49]Gazdhar A,Susuri N,Hostettler K,et al.HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic.PLoS One.2013;8(6):e65453.
[50]Tuder RM,Yun JH.Vascular endothelial growth factor of the lung:friend or foe.Curr Opin Pharmacol.2008;8(3):255-260.
[51]Guan XJ,Song L,Han FF,et al.Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors.J Cell Biochem.2013;114(2):323-335.
[52]Chen YB,Lan YW,Hung TH,et al.Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model.Cell Stress Chaperones.2015;20(4):643-652.
[53]Liu S,Liu D,Chen C,et al.MSC Transplantation Improves Osteopenia via Epigenetic Regulation of Notch Signaling in Lupus.Cell Metab.2015;22(4):606-618.
[54]Yuan Y,Shi M,Li L,et al.Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1αpathway.Clin Sci(Lond).2016;130(23):2181-2198.
[55]和法莲.人脐带间充质干细胞对小鼠老年性器官功能退变的治疗作用及其机制研究[D].昆明:昆明医科大学,2017.
[56]Vizoso FJ,Eiro N,Cid S,et al.Mesenchymal Stem Cell Secretome:Toward Cell-Free Therapeutic Strategies in Regenerative Medicine.Int J Mol Sci.2017;18(9):E1852.
[57]Gupta N,Su X,Popov B,et al.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice.JImmunol.2007;179(3):1855-1863.
[58]Li X,Wang Y,An G,et al.Bone marrow mesenchymal stem cells attenuate silica-induced pulmonary fibrosis via paracrine mechanisms.Toxicol Lett.2017;270:96-107.
[59]Liu HM,Liu YT,Zhang J,et al.Bone marrow mesenchymal stem cells ameliorate lung injury through anti-inflammatory and antibacterial effect in COPD mice.J Huazhong Univ Sci Technolog Med Sci.2017;37(4):496-504.
[60]Gu W,Song L,Li XM,et al.Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPKpathways.Sci Rep.2015;5:8733.
[61]Jackson MV,Morrison TJ,Doherty DF,et al.Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS.Stem Cells.2016;34(8):2210-2223.
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