期刊论文详细信息
Respiratory Research
Therapeutic effects of amniotic fluid-derived mesenchymal stromal cells on lung injury in rats with emphysema
Houquan Tao3  Xujun He3  Chun Chen2  Yingyu Ma3  Yingjie Xia3  Jianping Yan2  Wulin Xu2  Chao Gu1  Yaqing Li2 
[1] The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P.R. China;Department of Respiratory Medicine, Zhejiang Provincial People’s Hospital, No. 158, Shangtang Road, Hangzhou 310014, Zhejiang, P.R. China;Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, P.R. China
关键词: Pulmonary emphysema;    Chronic obstructive pulmonary disease;    Pneumocytes;    Amniotic fluid;    Mesenchymal stromal cells;   
Others  :  1137252
DOI  :  10.1186/s12931-014-0120-3
 received in 2014-06-28, accepted in 2014-09-30,  发布年份 2014
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【 摘 要 】

Background

In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. To treat COPD, it is crucial to repair damaged lung tissue and regenerate the lost alveoli. Type II alveolar epithelial cells (AECII) play a vital role in maintaining lung tissue repair, and amniotic fluid-derived mesenchymal stromal cells (AFMSCs) possess the characteristics of regular mesenchymal stromal cells. However, it remains untested whether transplantation of rat AFMSCs (rAFMSCs) might alleviate lung injury caused by emphysema by increasing the expression of surfactant protein (SP)A and SPC and inhibiting AECII apoptosis.

Methods

We analyzed the phenotypic characteristics, differentiation potential, and karyotype of rAFMSCs, which were isolated from pregnant Sprague–Dawley rats. Moreover, we examined the lung morphology and the expression levels of SPA and SPC in rats with emphysema after cigarette-smoke exposure and intratracheal lipopolysaccharide instillation and rAFMSC transplantation. The ability of rAFMSCs to differentiate was measured, and the apoptosis of AECII was evaluated.

Results

In rAFMSCs, the surface antigens CD29, CD44, CD73, CD90, CD105, and CD166 were expressed, but CD14, CD19, CD34, and CD45 were not detected; rAFMSCs also strongly expressed the mRNA of octamer-binding transcription factor 4, and the cells could be induced to differentiate into adipocytes and osteocytes. Furthermore, rAFMSC treatment up-regulated the levels of SPA, SPC, and thyroid transcription factor 1 and inhibited AECII apoptosis, and rAFMSCs appeared to be capable of differentiating into AECII-like cells. Lung injury caused by emphysema was alleviated after rAFMSC treatment.

Conclusions

rAFMSCs might differentiate into AECII-like cells or induce local regeneration of the lung alveolar epithelium in vivo after transplantation and thus could be used in COPD treatment and lung regenerative therapy.

【 授权许可】

   
2014 Li et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Burgel PR: Pathogenesis of chronic obstructive pulmonary disease. Presse Med 2009, 38:406-412.
  • [2]Mizutani N, Fuchikami J, Takahashi M, Nabe T, Yoshino S, Kohno S: Pulmonary emphysema induced by cigarette smoke solution and lipopolysaccharide in guinea pigs. Biol Pharm Bull 2009, 32:1559-1564.
  • [3]Siganaki M, Koutsopoulos AV, Neofytou E, Vlachaki E, Psarrou M, Soulitzis N, Pentilas N, Schiza S, Siafakas NM, Tzortzaki EG: Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients. Respir Res 2010, 11:46. BioMed Central Full Text
  • [4]Hoffman AM, Ingenito EP: Alveolar epithelial stem and progenitor cells, emerging evidence for their role in lung regeneration. Curr Med Chem 2012, 19:6003-6008.
  • [5]Whitsett JA, Wert SE, Weaver TE: Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 2010, 61:105-119.
  • [6]Bonfield TL, Caplan AI: Adult mesenchymal stem cells, an innovative therapeutic for lung diseases. Discov Med 2010, 9:337-345.
  • [7]Moodley Y, Manuelpillai U, Weiss DJ: Cellular therapies for lung disease, a distant horizon. Respirology 2011, 16:223-237.
  • [8]Sinclair K, Yerkovich ST, Chambers DC: Mesenchymal stem cells and the lung. Respirology 2013, 18:397-411.
  • [9]Giangreco A, Arwert EN, Rosewell IR, Snyder J, Watt FM, Stripp BR: Stem cells are dispensable for lung homeostasis but restore airways after injury. Proc Natl Acad Sci U S A 2009, 106:9286-9291.
  • [10]Conese M, Carbone A, Castellani S, Di Gioia S: Paracrine effects and heterogeneity of marrow-derived stem/progenitor cells, relevance for the treatment of respiratory diseases. Cells Tissues Organs 2013, 197:445-473.
  • [11]Gaur M, Ritner C, Sievers R, Pedersen A, Prasad M, Bernstein HS, Yeghiazarians Y: Timed inhibition of p38MAPK directs accelerated differentiation of human embryonic stem cells into cardiomyocytes. Cytotherapy 2010, 12:807-817.
  • [12]Muguruma K, Sasai Y: In vitro recapitulation of neural development using embryonic stem cells, from neurogenesis to histogenesis. Dev Growth Differ 2012, 54:349-357.
  • [13]Samadikuchaksaraei A, Bishop AE: Derivation and characterization of alveolar epithelial cells from murine embryonic stem cells in vitro. Methods Mol Biol 2006, 330:233-248.
  • [14]Wang D, Haviland DL, Burns AR, Zsigmond E, Wetsel RA: A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 2007, 104:4449-4454.
  • [15]Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA: Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007, 179:1855-1863.
  • [16]van Haaften T, Byrne R, Bonnet S, Rochefort GY, Akabutu J, Bouchentouf M, Rey-Parra GJ, Galipeau J, Haromy A, Eaton F, Chen M, Hashimoto K, Abley D, Korbutt G, Archer SL, Thébaud B: Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med 2009, 180:1131-1142.
  • [17]Loi R, Beckett T, Goncz KK, Suratt BT, Weiss DJ: Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells. Am J Respir Crit Care Med 2006, 173:171-179.
  • [18]Sueblinvong V, Loi R, Eisenhauer PL, Bernstein IM, Suratt BT, Spees JL, Weiss DJ: Derivation of lung epithelium from human cord blood-derived mesenchymal stem cells. Am J Respir Crit Care Med 2008, 177:701-711.
  • [19]Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A: Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 2009, 175:303-313.
  • [20]Zhen G, Xue Z, Zhao J, Gu N, Tang Z, Xu Y, Zhang Z: Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells. Cytotherapy 2010, 12:605-614.
  • [21]Huh JW, Kim SY, Lee JH, Lee JS, Van Ta Q, Kim M, Oh YM, Lee YS, Lee SD: Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am J Physiol Lung Cell Mol Physiol 2011, 301:L255-L266.
  • [22]Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI: Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol 2010, 299:L760-L770.
  • [23]Goodwin M, Sueblinvong V, Eisenhauer P, Ziats NP, LeClair L, Poynter ME, Steele C, Rincon M, Weiss DJ: Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice. Stem Cells 2011, 29:1137-1148.
  • [24]Lee SH, Jang AS, Kim YE, Cha JY, Kim TH, Jung S, Park SK, Lee YK, Won JH, Kim YH, Park CS: Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis. Respir Res 2010, 11:16. BioMed Central Full Text
  • [25]Kim ES, Chang YS, Choi SJ, Kim JK, Yoo HS, Ahn SY, Sung DK, Kim SY, Park YR, Park WS: Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice. Respir Res 2011, 12:108. BioMed Central Full Text
  • [26]Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP: A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 2013, 143:1590-1598.
  • [27]De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A: Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007, 25:100-106.
  • [28]Sun H, Feng K, Hu J, Soker S, Atala A, Ma PX: Osteogenic differentiation of human amniotic fluid-derived stem cells induced by bone morphogenetic protein-7 and enhanced by nanofibrous scaffolds. Biomaterials 2010, 31:1133-1139.
  • [29]Joo S, Ko IK, Atala A, Yoo JJ, Lee SJ: Amniotic fluid-derived stem cells in regenerative medicine research. Arch Pharm Res 2012, 35:271-280.
  • [30]Hartmann K, Raabe O, Wenisch S, Arnhold S: Amniotic fluid derived stem cells give rise to neuron-like cells without a further differentiation potential into retina-like cells. Am J Stem Cells 2013, 2:108-118.
  • [31]Sessarego N, Parodi A, Podestà M, Benvenuto F, Mogni M, Raviolo V, Lituania M, Kunkl A, Ferlazzo G, Bricarelli FD, Uccelli A, Frassoni F: Multipotent mesenchymal stromal cells from amniotic fluid, solid perspectives for clinical application. Haematologica 2008, 93:339-346.
  • [32]Cananzi M, Atala A, De Coppi P: Stem cells derived from amniotic fluid, new potentials in regenerative medicine. Reprod Biomed Online 2009, 18:17-27.
  • [33]Carraro G, Perin L, Sedrakyan S, Giuliani S, Tiozzo C, Lee J, Turcatel G, De Langhe SP, Driscoll B, Bellusci S, Minoo P, Atala A, De Filippo RE, Warburton D: Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages. Stem Cells 2008, 26:2902-2911.
  • [34]Roubelakis MG, Trohatou O, Anagnou NP: Amniotic fluid and amniotic membrane stem cells, marker discovery. Stem Cells Int 2012, 2012:107836.
  • [35]Li Y, Xu W, Yan J, Xia Y, Gu C, Ma Y, Tao H: Differentiation of human amniotic fluid-derived mesenchymal stem cells into type II alveolar epithelial cells in vitro. Int J Mol Med 2014, 33:1507-1513.
  • [36]Pan HC, Cheng FC, Chen CJ, Lai SZ, Lee CW, Yang DY, Chang MH, Ho SP: Post-injury regeneration in rat sciatic nerve facilitated by neurotrophic factors secreted by amniotic fluid mesenchymal stem cells. J Clin Neurosci 2007, 14:1089-1098.
  • [37]Zheng YB, Zhang XH, Huang ZL, Lin CS, Lai J, Gu YR, Lin BL, Xie DY, Xie SB, Peng L, Gao ZL: Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure. PLoS One 2012, 7:e41392.
  • [38]Colosimo A, Russo V, Mauro A, Curini V, Marchisio M, Bernabò N, Alfonsi M, Mattioli M, Barboni B: Prolonged in vitro expansion partially affects phenotypic features and osteogenic potential of ovine amniotic fluid-derived mesenchymal stromal cells. Cytotherapy 2013, 15:930-950.
  • [39]Zheng H, Liu Y, Huang T, Fang Z, Li G, He S: Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke. Toxicol Lett 2009, 189:225-234.
  • [40]Jiang H, Zhu Y, Xu H, Sun Y, Li Q: Activation of hypoxia-inducible factor-1alpha via nuclear factor-kappa B in rats with chronic obstructive pulmonary disease. Acta Biochim Biophys Sin (Shanghai) 2010, 42:483-488.
  • [41]Agarwal AR, Yin F, Cadenas E: Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells. Am J Respir Cell Mol Biol 2014, 51:284-293.
  • [42]Li YQ, Yan JP, Xu WL, Wang H, Xia YJ, Wang HJ, Zhu YY, Huang XJ: ADAM17 mediates MMP9 expression in lung epithelial cell. PLoS One 2013, 8:e51701.
  • [43]Farkas L, Farkas D, Warburton D, Gauldie J, Shi W, Stampfli MR, Voelkel NF, Kolb M: Cigarette smoke exposure aggravates air space enlargement and alveolar cell apoptosis in Smad3 knockout mice. Am J Physiol Lung Cell Mol Physiol 2011, 301:L391-L401.
  • [44]Macnee W: Pathogenesis of chronic obstructive pulmonary disease. Clin Chest Med 2007, 28:479-513.
  • [45]Martin TR: Recognition of bacterial endotoxin in the lungs. Am J Respir Cell Mol Biol 2000, 23:128-132.
  • [46]Sun D, Bu L, Liu C, Yin Z, Zhou X, Li X, Xiao A: Therapeutic effects of human amniotic fluid-derived stem cells on renal interstitial fibrosis in a murine model of unilateral ureteral obstruction. PLoS One 2013, 8:e65042.
  • [47]Donovan PJ: High Oct-ane fuel powers the stem cell. Nat Genet 2001, 29:246-247.
  • [48]Pesce M, Gross MK, Schöler HR: In line with our ancestors, Oct-4 and the mammalian germ. Bioessays 1998, 20:722-732.
  • [49]Prusa AR, Marton E, Rosner M, Bernaschek G, Hengstschläger M: Oct-4-expressing cells in human amniotic fluid, a new source for stem cell research? Hum Reprod 2003, 18:1489-1493.
  • [50]Jomura S, Uy M, Mitchell K, Dallasen R, Bode CJ, Xu Y: Potential treatment of cerebral global ischemia with Oct-4+ umbilical cord matrix cells. Stem Cells 2007, 25:98-106.
  • [51]Tondeur S, Assou S, Nadal L, Hamamah S, De Vos J: Biology and potential of human embryonic stem cells. Ann Biol Clin (Paris) 2008, 66:241-247.
  • [52]Goldmann T, Kähler D, Schultz H, Abdullah M, Lang DS, Stellmacher F, Vollmer E: On the significance of Surfactant Protein-A within the human lungs. Diagn Pathol 2009, 4:8. BioMed Central Full Text
  • [53]Fujino N, Kubo H, Suzuki T, Ota C, Hegab AE, He M, Suzuki S, Suzuki T, Yamada M, Kondo T, Kato H, Yamaya M: Isolation of alveolar epithelial type II progenitor cells from adult human lungs. Lab Invest 2011, 91:363-378.
  • [54]Buckley S, Shi W, Carraro G, Sedrakyan S, Da Sacco S, Driscoll BA, Perin L, De Filippo RE, Warburton D: The milieu of damaged alveolar epithelial type 2 cells stimulates alveolar wound repair by endogenous and exogenous progenitors. Am J Respir Cell Mol Biol 2011, 45:1212-1221.
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