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

Experimental Lung Research

Volumn 39, Issue 8, 2013, Pages 315-327

  Inamdar, Ajinkya C ^a   Inamdar, Arati A ^a,b  

^a Saiseva Biotech Pvt Ltd   (India)

^b RUTGERS UNIVERSITY   (United States)

Author keywords

Fibrosis; Immune response; Infection; Inflammation; Regeneration

Indexed keywords

CORTICOSTEROID; REMESTEMCEL L;

ACUTE GRAFT VERSUS HOST DISEASE; ADULT RESPIRATORY DISTRESS SYNDROME; ASTHMA; AUTOIMMUNE DISEASE; CELL HOMING; CELL REGENERATION; CHRONIC OBSTRUCTIVE LUNG DISEASE; DOWN REGULATION; HUMAN; INFLAMMATION; INTERSTITIAL LUNG DISEASE; LUNG DISEASE; LUNG FIBROSIS; MESENCHYMAL STEM CELL; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW;

ANIMALS; ASTHMA; AUTOIMMUNE DISEASES; BACTERIAL INFECTIONS; CELL MOVEMENT; HUMANS; HYPERTENSION, PULMONARY; INFUSIONS, INTRAVENOUS; LUNG DISEASES; LUNG DISEASES, INTERSTITIAL; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; PNEUMONIA; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; REGENERATION; RESPIRATORY DISTRESS SYNDROME, ADULT;

EID: 84885087642     PISSN: 01902148     EISSN: 15210499     Source Type: Journal    
DOI: 10.3109/01902148.2013.816803     Document Type: Review

References (121)

1. Bonfield T, Caplan A: Adult mesenchymal stem cells: An innovative therapeutic for lung diseases. Discov Med. 2010;9:337-345
2. Moodley Y, Manuelpillai U, Weiss DJ: Cellular therapies for lung disease: A distant horizon. Respirology. 2011;16:223-237
3. Sinclair K, Yerkovich S T, Chambers DC: Mesenchymal stem cells and the lung. Respirology. 2013;18:397-411
4. 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
5. Busse WW, Calhoun WF, Sedgwick JD: Mechanism of airway inflammation in asthma. Am Rev Respir Dis. 1993; 147:S20-S24
6. BarnerM,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
7. 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
8. AkbariO, Freeman GJ,Meyer EH,Greenfield EA, Chang TT, Sharpe AH, Berry G, DeKruyff RH, Umetsu DT: Antigenspecific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nature Med. 2002;8:1024-1032
9. 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
10. Berger P, Girodet PO, Manuel Tunon-de-Lara J: Mast cell myositis: A new feature of allergic asthmä Allergy. 2005;60:1238-1240
11. 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
12. Force ADT: Acute respiratory distress syndrome. JAMA 2012;307:2526-2533
13. 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
14. Rinaldo JE: Mediation of ARDS by leukocytes. Clinical evidence and implications for therapy. CHEST J. 1986;89:590-593
15. 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
16. 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
17. 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
18. 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
19. Miller E, Cohen A, Nagao S, Griffith D, Maunder R, Martin T,Weiner-Kronish JP, SticherlingM,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 increasedmortality. AmJ Respir Crit Care Med. 1992;146:427-432
20. 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
21. Allen TC, Fudala R, Sandra EN, Kurdowska A: Antiinterleukin 8 autoantibody: Interleukin 8 immune complexes visualized by laser confocal microscopy in injured lung. Arch Pathol Lab Med. 2007;131:452-456
22. Shute JK, Vrugt B, Lindley I, Holgate ST, Bron A, Aalbers R, Djukanovíc R: Free and complexed interleukin-8 in blood and bronchial mucosa in asthma. Am J Respir Crit Care Med. 1997;155:1877-1883
23. 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
24. 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
25. Mossman BT, Churg A: Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med. 1998;157:1666-1680
26. Camus P, Fanton A, Bonniaud P, Camus C, Foucher P: Interstitial lung disease induced by drugs and radiation. Respiration. 2004;71:301-326
27. 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
28. 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
29. 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
30. 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
31. 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
32. 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
33. Brantly M, Nukiwa T, Crystal RG: Molecular basis of alpha- 1-Antitrypsin deficiency. Am J Med. 1988;84:13-31
34. 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
35. 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
36. 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
37. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD: Requirement for macrophage elastase for cigarette smokeinduced emphysema in mice. Science. 1997;277:2002-2004
38. 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
39. 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
40. 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
41. Gebler A, Zabel O, Seliger B: The immunomodulatory capacity of mesenchymal stem cells. Trends in Molecular Medicine. 2012;18:128-134
42. 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
43. 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
44. 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
45. 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
46. Moodley Y, Atienza D, ManuelpillaiU, SamuelCS, 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
47. 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-derivedMSCs 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
48. 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
49. 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
50. EpperlyMW, 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
51. 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
52. 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 marrowderived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: Results of a phase I study. Gut. 2010;59:1662-1669
53. 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 andMarrow 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
54. 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
55. 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
56. 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
57. 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
58. 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
59. Baksh D, Yao R, Tuan RS: Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bonemarrow. Stem Cells. 2007;25:1384-1392
60. 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
61. 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
62. 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
63. Karahuseyinoglu S, CinarO,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
64. 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
65. Ribeiro CA, Fraga JS, Gräos 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
66. 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
67. 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
68. 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
69. 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
70. Katsha AM, Ohkouchi S, Xin H, KanehiraM, 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
71. Huh JW, Kim SY, Lee JH, Lee JS, Van Ta Q, Kim M, Oh YM, Lee YS, Lee SD: Bone marrow cells repair cigarette smokeinduced emphysema in rats. Am J Physiol Lung Cell Mol Physiol. 2011;301:L255-L266
72. 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
73. 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
74. Schweitzer KS, Johnstone BH, Garrison J, RushNI, 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
75. 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
76. 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
77. 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 TGFbeta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Nat Acad Sci USA. 2010;107: 5652-5657
78. 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
79. Kavanagh H, Mahon BP: Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy. 2011;66:523-531
80. 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
81. 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
82. 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
83. 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
84. 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
85. 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
86. 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
87. 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
88. 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
89. 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
90. 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
91. 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
92. Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA: Antibacterial effect of humanmesenchymal stem cells Is ediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 2010;28:2229-2238
93. 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
94. 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
95. 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
96. 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
97. 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
98. 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
99. 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
100. 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
101. 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
102. 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-derivedMSCs 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
103. Baber SR, Deng W, Master RG, Bunnell BA, Taylor BK, Murthy SN, Hyman AL, Kadowitz PJ: Intratracheal mesenchymal stem cell administration attenuates monocrotalineinduced pulmonary hypertension and endothelial dysfunction. Am J Physiol Lung Cell Mol Physiol. 2007;292: H1120-H1128
104. 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
105. 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
106. 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
107. 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
108. 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
109. 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
110. 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
111. 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
112. 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
113. 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
114. Collins K, Mitchell JR: Telomerase in the human organism. Oncogene. 2002;21:564
115. Flores I, Benetti R, Blasco MA: Telomerase regulation and stem cell behaviour. Curr Opin Cell Biol. 2006;18:254-260
116. 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
117. 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
118. 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
119. 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, LundbergK: Specific interaction between genotype, smoking and autoimmunity to citrullinated α-enolase in the etiology of rheumatoid arthritis. Nat Genet. 2009;41:1319-1324
120. EricssonUB, 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
121. Hudson M, Lo E, Lu Y, HerczD, Baron M, Steele R: Cigarette smoking in patients with systemic sclerosis. Arthritis Rheum. 2011;63:230-238