1,034
Views
50
CrossRef citations to date
0
Altmetric
REVIEW

Mesenchymal stem cell therapy in lung disorders: Pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell

&
Pages 315-327 | Received 11 Jan 2013, Accepted 14 Jun 2013, Published online: 30 Aug 2013

REFERENCES

  • Bonfield T, Caplan A: Adult mesenchymal stem cells: an innovative therapeutic for lung diseases. Discov Med. 2010;9:337–345.
  • Moodley Y, Manuelpillai U, Weiss DJ: Cellular therapies for lung disease: a distant horizon. Respirology. 2011;16:223–237.
  • Sinclair K, Yerkovich S T, Chambers DC: Mesenchymal stem cells and the lung. Respirology. 2013;18:397–411.
  • Karagiannidis C, Hense G, Martin C, Epstein M, Rückert B, Mantel PY, Menz G, Uhlig S, Blaser K, Schmidt-Weber CB: Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β–mediated airway remodeling in asthma. J Allergy Clin Immunol. 2006;117:111–118.
  • Busse WW, Calhoun WF, Sedgwick JD: Mechanism of airway inflammation in asthma. Am Rev Respir Dis. 1993; 147:S20–S24.
  • Barner M, Mohrs M, Brombacher F, Kopf M: Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Curr Biol.: CB. 1998;8:669–672.
  • Nakajima H, Iwamoto I, Tomoe S, Matsumura R, Tomioka H, Takatsu K, Yoshida S: CD4 +T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis. 1992;146:374–377.
  • Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, Berry G, DeKruyff RH, Umetsu DT: Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nature Med. 2002;8:1024–1032.
  • Lee SH, Jang AS, Kwon JH, Park SK, Won JH, Park CS: Mesenchymal stem cell transfer suppresses airway remodeling in a toluene diisocyanate-induced murine asthma model. Allergy, Asthma & Immunology Research. 2011;3:205–211.
  • Berger P, Girodet PO, Manuel Tunon-de-Lara J: Mast cell myositis: a new feature of allergic asthma? Allergy. 2005;60:1238–1240.
  • Berger P, Girodet PO, Begueret H, Ousova O, Perng DW, Marthan R, Walls AF, Tunon de Lara JM: Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J. 2003;17:2139–2141.
  • Force ADT: Acute respiratory distress syndrome. JAMA 2012;307:2526–2533.
  • Pierrakos C, Karanikolas M, Scolletta S, Karamouzos V, Velissaris D: Acute respiratory distress syndrome: pathophysiology and therapeutic options. J Clin Med Res. 2012;4:7–16.
  • Rinaldo JE: Mediation of ARDS by leukocytes. Clinical evidence and implications for therapy. CHEST J. 1986;89:590–593.
  • Weiland JE, Davis WB, Holter JF, Mohammed J, Dorinsky P, Gadek J: Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis. 1986;133:218.
  • Martin TR, Pistorese BP, Hudson LD, Maunder RJ: The function of lung and blood neutrophils in patients with the adult respiratory distress syndrome: implications for the pathogenesis of lung infections. Am J Respir Crit Care Med. 1991;144:254–262.
  • Ishitsuka Y, Moriuchi H, Isohama Y, Tokunaga H, Hatamoto K, Kurita S, Irikura M, Iyama K, Irie T: A selective thromboxane A2 (TXA2) synthase inhibitor, ozagrel, attenuates lung injury and decreases monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in oleic acid-induced lung injury in guinea pigs. J Pharmacol Sci. 2009;111:211–215.
  • Goodman RB, Strieter RM, Martin DP, Steinberg KP, Milberg JA, Maunder RJ, Kunkel SL, Walz A, Hudson LD, Martin TR: Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1996;154:602–611.
  • Miller E, Cohen A, Nagao S, Griffith D, Maunder R, Martin T, Weiner-Kronish JP, Sticherling M, Christophers E, Matthay MA: Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am J Respir Crit Care Med. 1992;146:427–432.
  • Fudala R, Krupa A, Stankowska D, Allen T, Kurdowska A. Anti-interleukin-8 autoantibody: interleukin-8 immune complexes in acute lung injury/acute respiratory distress syndrome. Clin Sc. 2008;114:403–412.
  • Allen TC, Fudala R, Sandra EN, Kurdowska A: Anti-interleukin 8 autoantibody: interleukin 8 immune complexes visualized by laser confocal microscopy in injured lung. Arch Pathol Lab Med. 2007;131:452–456.
  • Shute JK, Vrugt B, Lindley I, Holgate ST, Bron A, Aalbers R, Djukanović R: Free and complexed interleukin-8 in blood and bronchial mucosa in asthma. Am J Respir Crit Care Med. 1997;155:1877–1883.
  • Peichl P, Pursch E, Bröll H, Lindley I. Anti-IL-8 autoantibodies and complexes in rheumatoid arthritis: polyclonal activation in chronic synovial tissue inflammation. Rheumatol Int. 1999;18:141–145.
  • Kurdowska A, Noble JM, Steinberg KP, Ruzinski JT, Hudson LD, Martin TR. Anti-interleukin 8 autoantibody: interleukin 8 complexes in the acute respiratory distress syndrome relationship between the complexes and clinical disease activity. Am J Respir Crit Care Med. 2001;163:463–468.
  • Mossman BT, Churg A: Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med. 1998;157:1666–1680.
  • Camus P, Fanton A, Bonniaud P, Camus C, Foucher P: Interstitial lung disease induced by drugs and radiation. Respiration. 2004;71:301–326.
  • Trulock EP, Edwards LB, Taylor DO, Boucek MM, Mohacsi PJ, Keck BM, Hertz MI: The Registry of the International Society for Heart and Lung Transplantation: twentieth official adult lung and heart–lung transplant report—2003. J Heart Lung Transplant. 2003;22:625–635.
  • Hagimoto N, Kuwano K, Nomoto Y, Kunitake R, Hara N: Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. Am J Respir Cell Mol Biol. 1997;16:91.
  • Piguet PF, Collart MA, Grau GE, Kapanci Y, Vassalli P: Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis. J Exp Med. 1989;170:655–663.
  • Sapey E, Stockley JA, Greenwood H, Ahmad A, Bayley D, Lord JM, Insall RH, Stockley RA: Behavioral and structural differences in migrating peripheral neutrophils from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183:1176–1186.
  • Nakajima T, Owen CA: Polymorphonuclear neutrophils move into the fast lane in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183:1118–1120.
  • Retamales I, Elliott WM, Meshi B, Coxson HO, Pare PD, Sciurba FC, Rogers RM, Hayashi S, Hogg JC: Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med. 2001;164:469–473.
  • Brantly M, Nukiwa T, Crystal RG: Molecular basis of alpha-1-antitrypsin deficiency. Am J Med. 1988;84:13–31.
  • D'Armiento J, Dalal SS, Okada Y, Berg RA, Chada K: Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell. 1992;71:955–961.
  • Ohnishi K, Takagi M, Kurokawa Y, Satomi S, Konttinen YT: Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest. 1998;78:1077.
  • Molet S, Belleguic C, Lena H, Germain N, Bertrand C, Shapiro S, Planquois JM, Delaval P, Lagente V: Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease. Inflamm Res. 2005;54:31–36.
  • Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD: Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002–2004.
  • Foronjy RF, Okada Y, Cole R, D'Armiento J: Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung. Am J Physiol Lung Cell Mol Physiol. 2003;284:L727–L737.
  • Vuillemenot BR, Rodriguez JF, Hoyle GW: Lymphoid tissue and emphysema in the lungs of transgenic mice inducibly expressing tumor necrosis factor-alpha. Am J Respir Cell Mol Biol. 2004;30:438–448.
  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–317.
  • Gebler A, Zabel O, Seliger B: The immunomodulatory capacity of mesenchymal stem cells. Trends in Molecular Medicine. 2012;18:128–134.
  • Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D, McIntosh KR: Immune properties of human umbilical cord wharton's jelly—Derived cells. Stem Cells. 2008;26:2865–2874.
  • Glennie S, Soeiro I, Dyson PJ, Lam EWF, Dazzi F: Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005;105:2821–2827.
  • 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.
  • 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.
  • 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.
  • Liu AR, Liu L, Chen S, Yang Y, Zhao HJ, Liu L, Guo FM, Lu XM, Qiu HB: 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;228:1270–1283.
  • Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA, Leor J: Systemic delivery of bone marrow–derived mesenchymal stem cells to the infarcted myocardium. Circulation. 2003;108:863–868.
  • Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ: Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5: 54–63.
  • Epperly MW, Guo H, Gretton JE, Greenberger JS: Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 2003;29:213–224.
  • Yan X, Liu Y, Han Q, Jia M, Liao L, Qi M, Zhao RC: Injured microenvironment directly guides the differentiation of engrafted Flk-1(1) mesenchymal stem cell in lung. Exp Hematol. 2007;35:1466–1475.
  • Duijvestein M, Vos ACW, Roelofs H, Wildenberg ME, Wendrich BB, Verspaget HW, Kooy-Winkelaar EM, Koning F, Zwaginga JJ, Fidder HH, Verhaar AP, Fibbe WE, van den Brink GR, Hommes DW: Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study. Gut. 2010;59:1662–1669.
  • Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O; Developmental Committee of the European Group for Blood and Marrow Transplantation: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. The Lancet. 2008;371:1579–1586.
  • Ringdén O: Mesenchymal stem cells for treatment and prevention of graft-versus-host disease and graft failure after hematopoietic stem cell transplantation and future challenges. Mesenchymal Stem Cell Therapy. 2013;174.
  • Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S: Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010;67:1187–1194.
  • Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP: A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest J Chest 2013;143:1590–1598.
  • Lu LL, Liu YJ, Yang SG, Zhao QJ, Wang X, Gong W, Han ZB, Xu ZS, Lu YX, Liu D, Chen ZZ, Han ZC: Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica. 2006;91:1017–1026.
  • Wu LF, Wang NN, Liu YS, Wei X: Differentiation of Wharton's jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells. Tissue Engineering Part A. 2009;15:2865–2873.
  • Baksh D, Yao R, Tuan RS: Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25:1384–1392.
  • Subramanian A, Shu-Uin G, Kae-Siang N, Gauthaman K, Biswas A, Choolani M, Bongso A, Chui-Yee F: Human umbilical cord Wharton's jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. J Cell Biochem. 2012;113:1886–1895.
  • Fong C, Richards M, Manasi N, Biswas A, Bongso A: Comparative growth behaviour and characterization of stem cells from human Wharton's jelly. Reproductive Biomedicine Online. 2007;15:708–718.
  • Zhang YN, Lie PC, Wei X: Differentiation of mesenchymal stromal cells derived from umbilical cord Wharton's jelly into hepatocyte-like cells. Cytotherapy. 2009;11:548–558.
  • Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DÖ, Tukun A, Uckan D, Can A: Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells. 2006;25:319–331.
  • Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC: Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells. 2004;22:1330–1337.
  • Ribeiro CA, Fraga JS, Grãos M, Neves NM, Reis RL, Gimble JM, Sousa N, Salgado AJ: The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations. Stem Cell Research & Therapy. 2012;3:18.
  • Stolzing A, Jones E, McGonagle D, Scutt A: Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008;129:163–173.
  • Li J, Li D, Liu X, Tang S, Wei F: Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats. J Inflamm. 2012;9:33.
  • 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.
  • Guan XJ, Song L, Han FF, Cui ZI, Chen X, Guo XJ, Xu WG: Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors. J Cell Biochem 2013;114:323–335.
  • Katsha AM, Ohkouchi S, Xin H, Kanehira M, Sun R, Nukiwa T, Saijo Y: Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Molecular Therapy: The Journal of the American Society of Gene Therapy. 2011;19:196–203.
  • 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.
  • Zhen G, Liu H, Gu N, Zhang H, Xu Y, Zhang Z: Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Front Biosci: A Journal and Virtual Library. 2008;13:3415–3422.
  • 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.
  • Schweitzer KS, Johnstone BH, Garrison J, Rush NI, Cooper S, Traktuev DO, Feng D, Adamowicz JJ, Van Demark M, Fisher AJ, Kamocki K, Brown MB, Presson RG Jr, Broxmeyer HE, March KL, Petrache I: Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. Am J Respir Crit Care Med. 2011;183:215–225.
  • Furuya N, Takenaga M, Ohta Y, Tokura Y, Hamaguchi A, Sakamaki A, Kida H, Handa H, Nishine H, Mineshita M, Miyazawa T: Cell therapy with adipose tissue-derived stem/stromal cells for elastase-induced pulmonary emphysema in rats. Regenerative Med. 2012;7:503–512.
  • Ingenito EP, Tsai L, Murthy S, Tyagi S, Mazan M, Hoffman A: Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Cell Transplant. 2012;21:175–189.
  • Nemeth K, Keane-Myers A, Brown JM, Metcalfe DD, Gorham JD, Bundoc VG, Hodges MG, Jelinek I, Madala S, Karpati S, Mezey E: Bone marrowstromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Nat Acad Sci USA. 2010;107: 5652–5657.
  • 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.
  • Kavanagh H, Mahon BP: Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy. 2011;66:523–531.
  • 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.
  • Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D: Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase–mediated tryptophan degradation. Blood. 2004;103:4619–4621.
  • Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L: MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood. 2009;113:6576–6583.
  • Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L: Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood. 2006;107:1484–1490.
  • Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30:42–48.
  • Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A: Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107:367–372.
  • Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N: Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105:4120–4126.
  • Ramasamy R, Fazekasova H, Lam EWF, Soeiro I, Lombardi G, Dazzi F: Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation. 2007;83:71–76.
  • Abreu SC, Antunes MA, de Castro JC, de Oliveira MV, Bandeira E, Ornellas DS, Diaz BL, Morales MM, Xisto DG, Rocco PR: Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma. Respir Physiol Neurobiol. 2013;187(2):190–198.
  • Ortiz LA, DuTreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG: Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Nat Acad Sci. 2007;104:11002–11007.
  • Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J: Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2005;105:2214–2219.
  • Németh K, Leelahavanichkul A, Yuen PST, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E: Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production. Nature Med. 2008;15:42–49.
  • Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA: Antibacterial effect of human mesenchymal stem cells Is ediated in part from secretion of the antimicrobial peptide LL‐37. Stem Cells. 2010;28:2229–2238.
  • Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sørensen OE, Borregaard N, Rabe KF, Hiemstra PS: The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol. 2003;171:6690–6696.
  • Shi M, Li J, Liao L, Chen B, Li B, Chen L, Jia H, Zhao RC: Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica. 2007;92:897–904.
  • Ren G, Zhao X, Zhang L, Zhang J, L'Huillier A, Ling W, Roberts AI, Le AD, Shi S, Shao C, Shi Y: Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol. 2010;184:2321–2328.
  • Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG: Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Nat Acad Sci. 2003;100:8407–8411.
  • Ishizawa K, Kubo H, Yamada M, Kobayashi S, Suzuki T, Mizuno S, Nakamura T, Sasaki H: Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells. Biochem Biophys Res Commun. 2004;324:276–280.
  • Ishizawa K, Kubo H, Yamada M, Kobayashi S, Numasaki M, Ueda S, Suzuki T, Sasaki H: Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett. 2004;556:249–252.
  • Fehrenbach H, Kasper M, Tschernig T, Pan T, Schuh D, Shannon JM, Müller M, Mason RJ: Keratinocyte growth factor-induced hyperplasia of rat alveolar type II cells in vivo is resolved by differentiation into type I cells and by apoptosis. Eur Respir J: The Official Journal of the Europeon Society for Clinical Respiratory Physiology. 1999;14:534–544.
  • Curley GF, Hayes M, Ansari B, Shaw G, Ryan A, Barry F, O'Brien T, O'Toole D, Laffey JG: Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax. 2012;67:496–501.
  • Lee JW, Fang X, Gupta N, Serikov V, Matthay MA: Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Nat Acad Sci. 2009;106:16357–16362.
  • Liu AR, Liu L, Chen S, Yang Y, Zhao HJ, Liu L, Guo FM, Lu XM, Qiu HB: 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;228:1270–1283.
  • Baber SR, Deng W, Master RG, Bunnell BA, Taylor BK, Murthy SN, Hyman AL, Kadowitz PJ: Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Lung Cell Mol Physiol. 2007;292: H1120–H1128.
  • Patel KM, Crisostomo P, Lahm T, Markel T, Herring C, Wang M, Meldrum KK, Lillemoe KD, Meldrum DR: Mesenchymal stem cells attenuate hypoxic pulmonary vasoconstriction by a paracrine mechanism. J Surgical Res. 2007;143:281–285.
  • Umar S, de Visser YP, Steendijk P, Schutte CI, Wagenaar GTM, Bax WH, Mantikou E, Pijnappels DA, Atsma DE, Schalij MJ, van der Wall EE, van der Laarse A: Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2009;297:H1606–H1616.
  • 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. Respiratory Res. 2010;11:16.
  • Zhao DC, Lei JX, Chen R, Yu WH, Zhang XM, Li SN, Xiang P: Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol. 2005;11:3431.
  • Christopeit M, Schendel M, Föll J, Müller L, Keysser G, Behre G: Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L. Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, UK. 2007;22:1062–1064.
  • Cho KA, Woo SY, Seoh JY, Han HS, Ryu KH: Mesenchymal stem cells restore CCl4-induced liver injury by an antioxidative process. Cell Biol Int. 2012;36:1267–1274.
  • Lee C, Mitsialis SA, Aslam M, Vitali SH, Vergadi E, Konstantinou G, Sdrimas K, Fernandez-Gonzalez A, Kourembanas S: Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012;126:2601–2611.
  • Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, Rowlands DJ, Quadri SK, Bhattacharya S, Bhattacharya J: Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nature Med. 2012;18:759–765.
  • Huang K, Rabold R, Schofield B, Mitzner W, Tankersley CG: Age-dependent changes of airway and lung parenchyma in C57BL/6J mice. J Appl Physiol. 2007;102:200–206.
  • Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL: Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005;33:145–152.
  • Collins K, Mitchell JR: Telomerase in the human organism. Oncogene. 2002;21:564.
  • Flores I, Benetti R, Blasco MA: Telomerase regulation and stem cell behaviour. Curr Opin Cell Biol. 2006;18:254–260.
  • Armanios MY, Chen JJL, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA 3rd, Lansdorp PM, Greider CW, Loyd JE: Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356:1317–1326.
  • Valdes A, Andrew T, Gardner J, Kimura M, Oelsner E, Cherkas L, Aviv A, Spector TD: Obesity, cigarette smoking, and telomere length in women. The Lancet. 2005;366: 662–664.
  • Katzenstein AL, Mukhopadhyay S, Zanardi C, Dexter E: Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Human Pathol. 2010;41:316–325.
  • Mahdi H, Fisher BA, Källberg H, Plant D, Malmström V, Rönnelid J, Charles P, Ding B, Alfredsson L, Padyukov L, Symmons DP, Venables PJ, Klareskog L, Lundberg K: Specific interaction between genotype, smoking and autoimmunity to citrullinated α-enolase in the etiology of rheumatoid arthritis. Nat Genet. 2009;41:1319–1324.
  • Ericsson UB, Lindgärde F: Effects of cigarette smoking on thyroid function and the prevalence of goitre, thyrotoxicosis and autoimmune thyroiditis. J Intern Med. 2009;229:67–71.
  • Hudson M, Lo E, Lu Y, Hercz D, Baron M, Steele R: Cigarette smoking in patients with systemic sclerosis. Arthritis Rheum. 2011;63:230–238.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.