Generic placeholder image

Current Stem Cell Research & Therapy

Author(s): Ning Ma, Mengwei Zhang, Guofeng Xu, Lifang Zhang, Min Luo, Meihua Luo, Xing Wang, Hongmei Tang, Xiaoyun Wang, Li Liu, Xiaolin Zhong, Jianguo Feng and Yuying Li*

DOI: 10.2174/1574888X18666230501234836

DownloadDownload PDF Flyer Cite As
Mesenchymal Stem Cell-derived Type II Alveolar Epithelial Progenitor Cells Attenuate LPS-induced Acute Lung Injury and Reduce P63 Expression

Page: [245 - 256] Pages: 12

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Aim: Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a severe clinical respiratory-failure disease mainly characterized by acute damage to the alveolar epithelium and pulmonary vascular endothelial cells. Stem cell therapy has emerged as a potential regenerative strategy for ARDS/ALI, however, the outcome is limited, and the underlying mechanisms are unclear.

Introduction: We established a differentiation system for bone marrow-derived mesenchymal stem cellderived (BM-MSC) type II alveolar epithelial progenitor cells (AECIIs) and assessed their regulatory effects on lipopolysaccharide (LPS)-induced ALI.

Methods: We induced BM-MSC differentiation into AECIIs using a specific conditioned medium. After 26 days of differentiation, 3×105 BM-MSC-AECIIs were used to treat mice with LPS-induced ALI through tracheal injection.

Results: After tracheal injection, BM-MSC-AECIIs migrated to the perialveolar area and reduced LPSinduced lung inflammation and pathological injury. RNA-seq suggested that P63 protein was involved in the effects of BM-MSC-AECIIs on lung inflammation.

Conclusion: Our results suggest that BM-MSC-AECIIs may reduce LPS-induced acute lung injury by decreasing P63 expression.

Keywords: Acute lung injury, LPS, mesenchymal stem cells, type II alveolar epithelial progenitor cells, P63, BM-MSCAECIIs.

Graphical Abstract

[1]
Lewandowski K. Epidemiological data challenge ARDS/ALI definition. Intensive Care Med 1999; 25(9): 884-6.
[http://dx.doi.org/10.1007/s001340050974] [PMID: 10501737]
[2]
Dos Santos CC. Advances in mechanisms of repair and remodelling in acute lung injury. Intensive Care Med 2008; 34(4): 619-30.
[http://dx.doi.org/10.1007/s00134-007-0963-x] [PMID: 18264692]
[3]
McVey M, Tabuchi A, Kuebler WM. Microparticles and acute lung injury. Am J Physiol Lung Cell Mol Physiol 2012; 303(5): L364-81.
[http://dx.doi.org/10.1152/ajplung.00354.2011] [PMID: 22728467]
[4]
Kumar V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Front Immunol 2020; 11: 1722.
[http://dx.doi.org/10.3389/fimmu.2020.01722] [PMID: 32849610]
[5]
Vassiliou AG, Kotanidou A, Dimopoulou I, Orfanos SE. Endothelial damage in acute respiratory distress syndrome. Int J Mol Sci 2020; 21(22): 8793.
[http://dx.doi.org/10.3390/ijms21228793] [PMID: 33233715]
[6]
Torres Acosta MA, Singer BD. Pathogenesis of COVID-19-induced ARDS: Implications for an ageing population. Eur Respir J 2020; 56(3): 2002049.
[http://dx.doi.org/10.1183/13993003.02049-2020] [PMID: 32747391]
[7]
Ruaro B, Salton F, Braga L, et al. The history and mystery of alveolar epithelial type II cells: Focus on their physiologic and pathologic role in lung. Int J Mol Sci 2021; 22(5): 2566.
[http://dx.doi.org/10.3390/ijms22052566] [PMID: 33806395]
[8]
Guillot L, Nathan N, Tabary O, et al. Alveolar epithelial cells: Master regulators of lung homeostasis. Int J Biochem Cell Biol 2013; 45(11): 2568-73.
[http://dx.doi.org/10.1016/j.biocel.2013.08.009] [PMID: 23988571]
[9]
Corvol H, Flamein F, Epaud R, Clement A, Guillot L. Lung alveolar epithelium and interstitial lung disease. Int J Biochem Cell Biol 2009; 41(8-9): 1643-51.
[http://dx.doi.org/10.1016/j.biocel.2009.02.009] [PMID: 19433305]
[10]
Guillamat-Prats R, Puig F, Camprubí-Rimblas M, et al. Intratracheal instillation of alveolar type II cells enhances recovery from acute lung injury in rats. J Heart Lung Transplant 2018; 37(6): 782-91.
[http://dx.doi.org/10.1016/j.healun.2017.10.025] [PMID: 29229270]
[11]
Wang Y, Tang Z, Huang H, et al. Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate. Proc Natl Acad Sci 2018; 115(10): 2407-12.
[http://dx.doi.org/10.1073/pnas.1719474115] [PMID: 29463737]
[12]
Kathiriya JJ, Brumwell AN, Jackson JR, Tang X, Chapman HA. Distinct airway epithelial stem cells hide among club cells but mobilize to promote alveolar regeneration. Cell Stem Cell 2020; 26(3): 346-358.e4.
[http://dx.doi.org/10.1016/j.stem.2019.12.014] [PMID: 31978363]
[13]
Aspal M, Zemans RL. Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration. Int J Mol Sci 2020; 21(9): 3188.
[http://dx.doi.org/10.3390/ijms21093188] [PMID: 32366033]
[14]
Nabhan AN, Brownfield DG, Harbury PB, Krasnow MA, Desai TJ. Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science 2018; 359(6380): 1118-23.
[http://dx.doi.org/10.1126/science.aam6603] [PMID: 29420258]
[15]
Barkauskas CE, Cronce MJ, Rackley CR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 2013; 123(7): 3025-36.
[http://dx.doi.org/10.1172/JCI68782] [PMID: 23921127]
[16]
Guillamat-Prats R, Camprubí-Rimblas M, Puig F, et al. Alveolar type II cells or mesenchymal stem cells: Comparison of two different cell therapies for the treatment of acute lung injury in rats. Cells 2020; 9(8): 1816.
[http://dx.doi.org/10.3390/cells9081816] [PMID: 32751857]
[17]
Hayes M, Curley G, Ansari B, Laffey JG. Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype? Crit Care 2012; 16(2): 205.
[http://dx.doi.org/10.1186/cc10570] [PMID: 22424108]
[18]
Chin JY, Koh Y, Joung KM, et al. The effects of hypothermia on endotoxin-primed lung. Anesth Analg 2007; 104(5): 1171-8.
[http://dx.doi.org/10.1213/01.ane.0000260316.95836.1c] [PMID: 17456669]
[19]
Yang C, Jiang J, Yang X, Wang H, Du J. Stem/progenitor cells in endogenous repairing responses: New toolbox for the treatment of acute lung injury. J Transl Med 2016; 14(1): 47.
[http://dx.doi.org/10.1186/s12967-016-0804-1] [PMID: 26865361]
[20]
Monsel A, Zhu Y, Gennai S, Hao Q, Liu J, Lee JW. Cell-based therapy for acute organ injury: Preclinical evidence and ongoing clinical trials using mesenchymal stem cells. Anesthesiology 2014; 121(5): 1099-121.
[http://dx.doi.org/10.1097/ALN.0000000000000446] [PMID: 25211170]
[21]
Serati-Nouri H, Rasoulpoor S, Pourpirali R, et al. In vitro expansion of human adipose-derived stem cells with delayed senescence through dual stage release of curcumin from mesoporous silica nanoparticles/electrospun nanofibers. Life Sci 2021; 285: 119947.
[http://dx.doi.org/10.1016/j.lfs.2021.119947] [PMID: 34530016]
[22]
Fernández-Francos S, Eiro N, González-Galiano N, Vizoso FJ. Mesenchymal stem cell-based therapy as an alternative to the treatment of acute respiratory distress syndrome: Current evidence and future perspectives. Int J Mol Sci 2021; 22(15): 7850.
[http://dx.doi.org/10.3390/ijms22157850] [PMID: 34360616]
[23]
Liu J, Peng D, You J, et al. Type 2 alveolar epithelial cells differentiated from human umbilical cord mesenchymal stem cells alleviate mouse pulmonary fibrosis through β-catenin-regulated cell apoptosis. Stem Cells Dev 2021; 30(13): 660-70.
[http://dx.doi.org/10.1089/scd.2020.0208] [PMID: 33899513]
[24]
Luca TYH, Sampada K, Marco PA, et al. Generation of an alveolar epithelial type II cell line from induced pluripotent stem cells. AM J PHYSIOL-LUNG C 2018; 315(6): L921-32.
[25]
Shafa M, Ionescu LI, Vadivel A, et al. Human induced pluripotent stem cell–derived lung progenitor and alveolar epithelial cells attenuate hyperoxia-induced lung injury. Cytotherapy 2018; 20(1): 108-25.
[http://dx.doi.org/10.1016/j.jcyt.2017.09.003] [PMID: 29056548]
[26]
El Agha E, Kramann R, Schneider RK, et al. Mesenchymal stem cells in fibrotic disease. Cell Stem Cell 2017; 21(2): 166-77.
[http://dx.doi.org/10.1016/j.stem.2017.07.011] [PMID: 28777943]
[27]
Yasamineh S, Kalajahi HG, Yasamineh P, et al. Spotlight on therapeutic efficiency of mesenchymal stem cells in viral infections with a focus on COVID-19. Stem Cell Res Ther 2022; 13(1): 257.
[http://dx.doi.org/10.1186/s13287-022-02944-7] [PMID: 35715852]
[28]
Zhang L, Guo K, Yin S, et al. RNA-Seq reveals underlying transcriptomic mechanisms of bone marrow-derived mesenchymal stem cells in the regulation of microglia-mediated neuroinflammation after subarachnoid hemorrhage. Stem Cells Dev 2020; 29(9): 562-73.
[http://dx.doi.org/10.1089/scd.2019.0216] [PMID: 31918626]
[29]
Aziz M, Ode Y, Zhou M, et al. B-1a cells protect mice from sepsis-induced acute lung injury. Mol Med 2018; 24(1): 26.
[http://dx.doi.org/10.1186/s10020-018-0029-2] [PMID: 30134811]
[30]
Barratt S, Creamer A, Hayton C, Chaudhuri N. Idiopathic pulmonary fibrosis (IPF): An overview. J Clin Med 2018; 7(8): 201.
[http://dx.doi.org/10.3390/jcm7080201] [PMID: 30082599]
[31]
Clerici C, Planès C. Gene regulation in the adaptive process to hypoxia in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 2009; 296(3): L267-74.
[http://dx.doi.org/10.1152/ajplung.90528.2008] [PMID: 19118091]
[32]
Chen L, Qu J, Kalyani FS, et al. Mesenchymal stem cell-based treatments for COVID-19: Status and future perspectives for clinical applications. Cell Mol Life Sci 2022; 79(3): 142.
[http://dx.doi.org/10.1007/s00018-021-04096-y] [PMID: 35187617]
[33]
Wilson JG, Liu KD, Zhuo H, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: A phase 1 clinical trial. Lancet Respir Med 2015; 3(1): 24-32.
[http://dx.doi.org/10.1016/S2213-2600(14)70291-7] [PMID: 25529339]
[34]
Zhang H, Cui Y, Zhou Z, Ding Y, Nie H. Alveolar type 2 epithelial cells as potential therapeutics for acute lung injury/acute respiratory distress syndrome. Curr Pharm Des 2020; 25(46): 4877-82.
[http://dx.doi.org/10.2174/1381612825666191204092456] [PMID: 31801451]
[35]
Wang D, Morales JE, Calame DG, Alcorn JL, Wetsel RA. Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. Mol Ther 2010; 18(3): 625-34.
[http://dx.doi.org/10.1038/mt.2009.317] [PMID: 20087316]
[36]
Dadashpour M, Pilehvar-Soltanahmadi Y, Zarghami N, Firouzi-Amandi A, Pourhassan-Moghaddam M, Nouri M. Emerging importance of phytochemicals in regulation of stem cells fate via signaling pathways. Phytother Res 2017; 31(11): 1651-68.
[http://dx.doi.org/10.1002/ptr.5908] [PMID: 28857315]
[37]
Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G. The p53/p63/p73 family of transcription factors: Overlapping and distinct functions. J Cell Sci 2000; 113(10): 1661-70.
[http://dx.doi.org/10.1242/jcs.113.10.1661] [PMID: 10769197]
[38]
Karsli Uzunbas G, Ahmed F, Sammons MA. Control of p53-dependent transcription and enhancer activity by the p53 family member p63. J Biol Chem 2019; 294(27): 10720-36.
[http://dx.doi.org/10.1074/jbc.RA119.007965] [PMID: 31113863]
[39]
Fisher ML, Balinth S, Mills AA. p63-related signaling at a glance. J Cell Sci 2020; 133(17): jcs228015.
[http://dx.doi.org/10.1242/jcs.228015] [PMID: 32917730]
[40]
Moses MA, George AL, Sakakibara N, et al. Molecular mechanisms of p63-mediated squamous cancer pathogenesis. Int J Mol Sci 2019; 20(14): 3590.
[http://dx.doi.org/10.3390/ijms20143590] [PMID: 31340447]
[41]
Kumar PA, Hu Y, Yamamoto Y, et al. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell 2011; 147(3): 525-38.
[http://dx.doi.org/10.1016/j.cell.2011.10.001] [PMID: 22036562]
[42]
Vaughan AE, Brumwell AN, Xi Y, et al. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 2015; 517(7536): 621-5.
[http://dx.doi.org/10.1038/nature14112] [PMID: 25533958]
[43]
Zuo W, Zhang T, Wu DZA, et al. p63+Krt5+ distal airway stem cells are essential for lung regeneration. Nature 2015; 517(7536): 616-20.
[http://dx.doi.org/10.1038/nature13903] [PMID: 25383540]
[44]
Chapman HA, Li X, Alexander JP, et al. Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice. J Clin Invest 2011; 121(7): 2855-62.
[http://dx.doi.org/10.1172/JCI57673] [PMID: 21701069]
[45]
Weiner AI, Zhao G, Zayas HM, et al. ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury. Cell Rep 2022; 41(11): 111805.
[http://dx.doi.org/10.1016/j.celrep.2022.111805] [PMID: 36516758]