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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Mesenchymal Stem Cell Therapy for ALI/ARDS: Therapeutic Potential and Challenges

Author(s): Zhenxing Wang, Tong Yu, Yapeng Hou, Wei Zhou, Yan Ding and Hongguang Nie*

Volume 28, Issue 27, 2022

Published on: 12 August, 2022

Page: [2234 - 2240] Pages: 7

DOI: 10.2174/1381612828666220707104356

Price: $65

Abstract

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a serious clinical common disease caused by various pathological factors and can induce serious complications. There is still no specific and effective method for the treatment of ALI/ARDS. Mesenchymal stem cells (MSCs) have been one of the treatment methods for ALI, which can regulate related signal pathways such as PI3K/AKT, Wnt, and NF-κB to reduce inflammation. MSCs exist in various tissues and can self-renewal and differentiation, which can be activated by specific substances or environments and home to the site of tissue damage, where they differentiate into new tissue cells and repair the damage. Both exosomes and cytokines involving the paracrine mechanism of MSCs have benefits in treating ALI. Lung organoids produced by 3D culture technology can simulate the lung's characteristics and help research the pathophysiological process of ALI. This review summarizes the mechanisms by which MSCs treat ALI/ARDS and expects to use 3D models for future challenges in this field.

Keywords: Mesenchymal stem cells, acute lung injury, acute respiratory distress syndrome, lung organoid, PI3K/AKT, hypoxemia.

« Previous Next »
[1]
Matthay MA, Zimmerman GA, Esmon C, et al. Future research directions in acute lung injury: Summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 2003; 167(7): 1027-35.
[http://dx.doi.org/10.1164/rccm.200208-966WS] [PMID: 12663342]
[2]
Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med 2017; 377(6): 562-72.
[http://dx.doi.org/10.1056/NEJMra1608077] [PMID: 28792873]
[3]
Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: The berlin definition. JAMA 2012; 307(23): 2526-33.
[PMID: 22797452]
[4]
Pouzol L, Sassi A, Baumlin N, et al. CXCR7 antagonism reduces acute lung injury pathogenesis. Front Pharmacol 2021; 12748740
[http://dx.doi.org/10.3389/fphar.2021.748740] [PMID: 34803691]
[5]
Matthay MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers 2019; 5(1): 18.
[http://dx.doi.org/10.1038/s41572-019-0069-0] [PMID: 30872586]
[6]
Phua J, Badia JR, Adhikari NK, et al. Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review. Am J Respir Crit Care Med 2009; 179(3): 220-7.
[http://dx.doi.org/10.1164/rccm.200805-722OC] [PMID: 19011152]
[7]
Herridge MS, Tansey CM, Matté A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011; 364(14): 1293-304.
[http://dx.doi.org/10.1056/NEJMoa1011802] [PMID: 21470008]
[8]
Zhang S, Danchuk SD, Bonvillain RW, et al. Interleukin 6 mediates the therapeutic effects of adipose-derived stromal/stem cells in lipopolysaccharide-induced acute lung injury. Stem Cells 2014; 32(6): 1616-28.
[http://dx.doi.org/10.1002/stem.1632] [PMID: 24449042]
[9]
Shi J, Yu J. PI3K/Akt pathway-mediated HO-1 induction regulates mitochondrial quality control and attenuates endotoxin-induced acute lung injury. Lab Invest 2019; 99: 1795-809.
[http://dx.doi.org/10.1038/s41374-019-0286-x] [PMID: 31570770]
[10]
Suo T, Chen GZ, Huang Y, Zhao KC, Wang T, Hu K. miRNA- 1246 suppresses acute lung injury-induced inflammation and apoptosis via the NF-κB and Wnt/β-catenin signal pathways. Biomed Pharmacother. 2018; 108: 783-91.
[http://dx.doi.org/10.1016/j.biopha.2018.09.046] [PMID: 30253370]
[11]
Lee JW, Fang X, Krasnodembskaya A, Howard JP, Matthay MA. Concise review: Mesenchymal stem cells for acute lung injury: Role of paracrine soluble factors. Stem Cells 2011; 29(6): 913-9.
[http://dx.doi.org/10.1002/stem.643] [PMID: 21506195]
[12]
Lässer C, Eldh M, Lötvall J. Isolation and characterization of RNA-containing exosomes. J Vis Exp 2012; 59e3037
[http://dx.doi.org/10.3791/3037] [PMID: 22257828]
[13]
Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA 2010; 107(14): 6328-33.
[http://dx.doi.org/10.1073/pnas.0914843107] [PMID: 20304794]
[14]
Park J, Kim S, Lim H, et al. Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia. Thorax 2019; 74(1): 43-50.
[http://dx.doi.org/10.1136/thoraxjnl-2018-211576] [PMID: 30076187]
[15]
Gazdic M, Volarevic V, Arsenijevic N, Stojkovic M. Mesenchymal stem cells: A friend or foe in immune-mediated diseases. Stem Cell Rev Rep 2015; 11(2): 280-7.
[http://dx.doi.org/10.1007/s12015-014-9583-3] [PMID: 25592610]
[16]
Xu T, Zhang Y, Chang P, Gong S, Shao L, Dong L. Mesenchymal stem cell-based therapy for radiation-induced lung injury. Stem Cell Res Ther 2018; 9(1): 18.
[http://dx.doi.org/10.1186/s13287-018-0776-6] [PMID: 29386045]
[17]
Han S, Mallampalli RK. The acute respiratory distress syndrome: From mechanism to translation. J Immunol 2015; 194(3): 855-60.
[http://dx.doi.org/10.4049/jimmunol.1402513] [PMID: 25596299]
[18]
Aghasafari P, George U, Pidaparti R. A review of inflammatory mechanism in airway diseases. Inflamm Res 2019; 68(1): 59-74.
[http://dx.doi.org/10.1007/s00011-018-1191-2] [PMID: 30306206]
[19]
Bentley JK, Popova AP, Bozyk PD, et al. Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype. Respir Res 2010; 11(1): 127.
[http://dx.doi.org/10.1186/1465-9921-11-127] [PMID: 20858250]
[20]
Zhu J, Feng B, Xu Y, et al. Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells. Cell Death Dis 2020; 11(10): 829.
[http://dx.doi.org/10.1038/s41419-020-03036-1] [PMID: 33024074]
[21]
Matthay MA, Robriquet L, Fang X. Alveolar epithelium: Role in lung fluid balance and acute lung injury. Proc Am Thorac Soc 2005; 2(3): 206-13.
[http://dx.doi.org/10.1513/pats.200501-009AC] [PMID: 16222039]
[22]
Franck T, Ceusters J, Graide H, Mouithys-Mickalad A, Serteyn D. Muscle derived mesenchymal stem cells inhibit the activity of the free and the neutrophil extracellular trap (NET)-bond myeloperoxidase. Cells 2021; 10(12): 3486.
[http://dx.doi.org/10.3390/cells10123486] [PMID: 34943996]
[23]
Cantrell DA. Phosphoinositide 3-kinase signalling pathways. J Cell Sci 2001; 114(Pt 8): 1439-45.
[http://dx.doi.org/10.1242/jcs.114.8.1439] [PMID: 11282020]
[24]
Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 2014; 26(12): 2694-701.
[http://dx.doi.org/10.1016/j.cellsig.2014.08.019] [PMID: 25173700]
[25]
Zhai C, Cheng J, Mujahid H, et al. Selective inhibition of PI3K/Akt/mTOR signaling pathway regulates autophagy of macrophage and vulnerability of atherosclerotic plaque. PLoS One 2014; 9(3)e90563
[http://dx.doi.org/10.1371/journal.pone.0090563] [PMID: 24599185]
[26]
Terman A, Brunk UT. Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc Res 2005; 68(3): 355-65.
[http://dx.doi.org/10.1016/j.cardiores.2005.08.014] [PMID: 16213475]
[27]
Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451(7182): 1069-75.
[http://dx.doi.org/10.1038/nature06639] [PMID: 18305538]
[28]
Li J, Huang S, Zhang J, et al. Mesenchymal stem cells ameliorate inflammatory cytokine-induced impairment of AT-II cells through a keratinocyte growth factor-dependent PI3K/Akt/mTOR signaling pathway. Mol Med Rep 2016; 13(5): 3755-62.
[http://dx.doi.org/10.3892/mmr.2016.5004] [PMID: 27035760]
[29]
Liu A, Chen S, Cai S, et al. Wnt5a through noncanonical Wnt/JNK or Wnt/PKC signaling contributes to the differentiation of mesenchymal stem cells into type II alveolar epithelial cells in vitro. PLoS One 2014; 9(3): e90229.
[http://dx.doi.org/10.1371/journal.pone.0090229] [PMID: 24658098]
[30]
Shi C, Lv T, Xiang Z, Sun Z, Qian W, Han X. Role of Wnt/β-catenin signaling in epithelial differentiation of lung resident mesenchymal stem cells. J Cell Biochem 2015; 116(8): 1532-9.
[http://dx.doi.org/10.1002/jcb.25069] [PMID: 25546504]
[31]
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004; 20(1): 781-810.
[http://dx.doi.org/10.1146/annurev.cellbio.20.010403.113126] [PMID: 15473860]
[32]
Wang Y, Sun Z, Qiu X, Li Y, Qin J, Han X. Roles of Wnt/beta-catenin signaling in epithelial differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 2009; 390(4): 1309-14.
[http://dx.doi.org/10.1016/j.bbrc.2009.10.143] [PMID: 19879238]
[33]
Cai SX, Liu AR, Chen S, et al. Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice. Stem Cell Res Ther 2015; 6(1): 65.
[http://dx.doi.org/10.1186/s13287-015-0060-y] [PMID: 25889393]
[34]
Liu AR, Liu L, Chen S, et al. Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro. J Cell Physiol 2013; 228(6): 1270-83.
[http://dx.doi.org/10.1002/jcp.24282] [PMID: 23154940]
[35]
Sun Z, Gong X, Zhu H, et al. Inhibition of Wnt/β-catenin signaling promotes engraftment of mesenchymal stem cells to repair lung injury. J Cell Physiol 2014; 229(2): 213-24.
[http://dx.doi.org/10.1002/jcp.24436] [PMID: 23881674]
[36]
Chopra M, Reuben JS, Sharma AC. Acute lung injury: Apoptosis and signaling mechanisms. Exp Biol Med (Maywood) 2009; 234(4): 361-71.
[http://dx.doi.org/10.3181/0811-MR-318] [PMID: 19176873]
[37]
Kupfner JG, Arcaroli JJ, Yum HK, Nadler SG, Yang KY, Abraham E. Role of NF-kappaB in endotoxemia-induced alterations of lung neutrophil apoptosis. J Immunol 2001; 167(12): 7044-51.
[http://dx.doi.org/10.4049/jimmunol.167.12.7044] [PMID: 11739525]
[38]
Su VY, Lin CS, Hung SC, Yang KY. Mesenchymal stem cell-conditioned medium induces neutrophil apoptosis associated with inhibition of the NF-κB pathway in endotoxin-induced acute lung injury. Int J Mol Sci 2019; 20(9): 2208.
[http://dx.doi.org/10.3390/ijms20092208]
[39]
Liu J, Chen T, Lei P, Tang X, Huang P. Exosomes released by bone marrow mesenchymal stem cells attenuate lung injury induced by intestinal ischemia reperfusion via the TLR4/NF-κB pathway. Int J Med Sci 2019; 16(9): 1238-44.
[http://dx.doi.org/10.7150/ijms.35369] [PMID: 31588189]
[40]
Li TJ, Zhao LL, Qiu J, Zhang HY, Bai GX, Chen L. Interleukin-17 antagonist attenuates lung inflammation through inhibition of the ERK1/2 and NF-κB pathway in LPS-induced acute lung injury. Mol Med Rep 2017; 16(2): 2225-32.
[http://dx.doi.org/10.3892/mmr.2017.6837] [PMID: 28656298]
[41]
Cárdenes N, Cáceres E, Romagnoli M, Rojas M. Mesenchymal stem cells: A promising therapy for the acute respiratory distress syndrome. Respiration 2013; 85(4): 267-78.
[http://dx.doi.org/10.1159/000347072] [PMID: 23428562]
[42]
Curley GF, Scott JA, Laffey JG. Therapeutic potential and mechanisms of action of mesenchymal stromal cells for acute respiratory distress syndrome. Curr Stem Cell Res Ther 2014; 9(4): 319-29.
[http://dx.doi.org/10.2174/1574888X09666140228144812] [PMID: 24588087]
[43]
Charbord P. Bone marrow mesenchymal stem cells: Historical overview and concepts. Hum Gene Ther 2010; 21(9): 1045-56.
[http://dx.doi.org/10.1089/hum.2010.115] [PMID: 20565251]
[44]
Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther 2014; 5(3): 76.
[http://dx.doi.org/10.1186/scrt465] [PMID: 24915963]
[45]
Ionescu L, Byrne RN, van Haaften T, et al. Stem cell conditioned medium improves acute lung injury in mice: In vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol 2012; 303(11): L967-77.
[http://dx.doi.org/10.1152/ajplung.00144.2011] [PMID: 23023971]
[46]
Rager TM, Olson JK, Zhou Y, Wang Y, Besner GE. Exosomes secreted from bone marrow-derived mesenchymal stem cells protect the intestines from experimental necrotizing enterocolitis. J Pediatr Surg 2016; 51(6): 942-7.
[http://dx.doi.org/10.1016/j.jpedsurg.2016.02.061] [PMID: 27015901]
[47]
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]
[48]
Sun J, Chen J, Cao J, Li T, Zhuang S, Jiang X. IL-1β-stimulated β-catenin up-regulation promotes angiogenesis in human lung-derived mesenchymal stromal cells through a NF-κB-dependent microRNA-433 induction. Oncotarget 2016; 7(37): 59429-40.
[http://dx.doi.org/10.18632/oncotarget.10683] [PMID: 27449086]
[49]
Yuan H, Guan J, Zhang J, Zhang R, Li M. Retracted: Exosomes secreted by human urine-derived stem cells accelerate skin wound healing by promoting angiogenesis in rat by Cell Biol Int 2017; 41(8): 933.
[http://dx.doi.org/10.1002/cbin.10615] [PMID: 27098397]
[50]
Akram KM, Samad S, Spiteri MA, Forsyth NR. Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms. Respir Res 2013; 14(1): 9.
[http://dx.doi.org/10.1186/1465-9921-14-9] [PMID: 23350749]
[51]
Fang X, Neyrinck AP, Matthay MA, Lee JW. Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1. J Biol Chem 2010; 285(34): 26211-22.
[http://dx.doi.org/10.1074/jbc.M110.119917] [PMID: 20554518]
[52]
Hayes M, Curley G, Laffey JG. Mesenchymal stem cells - a promising therapy for acute respiratory distress syndrome. F1000 Med Rep 2012; 4: 2.
[PMID: 22238514]
[53]
Li JW, Wu X. Mesenchymal stem cells ameliorate LPS-induced acute lung injury through KGF promoting alveolar fluid clearance of alveolar type II cells. Eur Rev Med Pharmacol Sci 2015; 19(13): 2368-78.
[PMID: 26214771]
[54]
Curley GF, Hayes M, Ansari B, et al. Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax 2012; 67(6): 496-501.
[http://dx.doi.org/10.1136/thoraxjnl-2011-201059] [PMID: 22106021]
[55]
Matthay MA, Thompson BT, Read EJ, et al. Therapeutic potential of mesenchymal stem cells for severe acute lung injury. Chest 2010; 138(4): 965-72.
[http://dx.doi.org/10.1378/chest.10-0518] [PMID: 20923800]
[56]
Yao L, Liu CJ, Luo Q, et al. Protection against hyperoxia-induced lung fibrosis by KGF-induced MSCs mobilization in neonatal rats. Pediatr Transplant 2013; 17(7): 676-82.
[http://dx.doi.org/10.1111/petr.12133] [PMID: 23919829]
[57]
Crisostomo PR, Wang Y, Markel TA, Wang M, Lahm T, Meldrum DR. Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. Am J Physiol Cell Physiol 2008; 294(3): C675-82.
[http://dx.doi.org/10.1152/ajpcell.00437.2007] [PMID: 18234850]
[58]
Kinnaird T, Stabile E, Burnett MS, et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109(12): 1543-9.
[http://dx.doi.org/10.1161/01.CIR.0000124062.31102.57] [PMID: 15023891]
[59]
Barratt S, Medford AR, Millar AB. Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. Respiration 2014; 87(4): 329-42.
[http://dx.doi.org/10.1159/000356034] [PMID: 24356493]
[60]
Clevers H. Modeling development and disease with organoids. Cell 2016; 165(7): 1586-97.
[http://dx.doi.org/10.1016/j.cell.2016.05.082] [PMID: 27315476]
[61]
Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL. Lung organoids: Current uses and future promise. Development 2017; 144: 986-97.
[http://dx.doi.org/10.1242/dev.140103] [PMID: 28292845]
[62]
Beers MF, Moodley Y. When is an alveolar type 2 cell an alveolar type 2 cell? A conundrum for lung stem cell biology and regenerative medicine. Am J Respir Cell Mol Biol 2017; 57(1): 18-27.
[http://dx.doi.org/10.1165/rcmb.2016-0426PS] [PMID: 28326803]
[63]
Griffin M, Bhandari R, Hamilton G, Chan YC, Powell JT. Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen. J Cell Sci 1993; 105(Pt 2): 423-32.
[http://dx.doi.org/10.1242/jcs.105.2.423] [PMID: 8408275]
[64]
Foster CD, Varghese LS, Skalina RB, Gonzales LW, Guttentag SH. In vitro transdifferentiation of human fetal type II cells toward a type I-like cell. Pediatr Res 2007; 61(4): 404-9.
[http://dx.doi.org/10.1203/pdr.0b013e3180332c6d] [PMID: 17515862]
[65]
Sucre JMS, Jetter CS, Loomans H, et al. Successful establishment of primary Ttype II alveolar epithelium with 3D organotypic coculture. Am J Respir Cell Mol Biol 2018; 59: 158-66.
[66]
Monsel A, Zhu YG, Gudapati V, Lim H, Lee JW. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther 2016; 16(7): 859-71.
[http://dx.doi.org/10.1517/14712598.2016.1170804] [PMID: 27011289]
[67]
Sdrimas K, Kourembanas S. MSC microvesicles for the treatment of lung disease: A new paradigm for cell-free therapy. Antioxid Redox Signal 2014; 21(13): 1905-15.
[http://dx.doi.org/10.1089/ars.2013.5784] [PMID: 24382303]
[68]
Leeman KT, Pessina P, Lee JH. Mesenchymal stem cells increase alveolar differentiation in lung progenitor organoid cultures. Sci Rep 2019; 9(1): 6479.
[http://dx.doi.org/10.1038/s41598-019-42819-1] [PMID: 31015509]

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