Abstract
Despite substantial clinical advances over the past decades, inflammatory lung diseases are a major cause of morbidity and mortality and have become one of the major public health issues across the world. The World Health Organization positions lung diseases second in epidemiology, mortality, and cost and predicts that about one-fifth deaths will be attributed to lung diseases by 2020. Currently, there are no therapeutic ways to inhibit or reverse the pathobiology of many destructive lung diseases that results in dysfunctional lung renovation. However, recent studies indicate that lung mesenchymal stem cells (MSCs) are triggered by local factors to differentiate into myofibroblasts that contribute to disease progression. Therefore, it is of critical significance to understand the molecular and cellular basis of endogenous lung MSCs participation in lung injury and repair. Interestingly, while the lung exhibits tremendous regenerative capacity, restoration of pulmonary function does not occur in many adult lung diseases. To address this condition emphasis has been increased on the development of cell-based therapies, but due to diverse cell types and functions lung is considered as a recalcitrant candidate for these strategies. Currently, origins and contributions of stem cells are under intense investigation for cell-based therapy and pulmonary remodelling. Specialized microenvironments for resident multipotent MSCs have been identified in many adult tissues and normal differentiation processes of these may be disrupted by pathologic micro-environmental stimuli during disease, epigenetic changes, or genetic alteration, which program their contribution to pathologic expansion at the expense of functional tissue regeneration. MSCs are most widely investigated and clinically tested type of stem cell because of their regenerative capacity to mesoderm/non-mesoderm-derived tissues and they also display immune-enhancing as well as immunosuppressive properties. MSCs especially from human are widely studied as compared to other cells, different early stage clinical and scientific studies show potential for repair and renewal of lung tissues and offer great ability for the treatment of several devastating and incurable lung diseases. Bone marrow derived MSCs (BM-MSCs) are currently tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases. Here, we will review the biology of MSCs, their interaction with molecular and cellular pathways, and their modulation of immune responses in lung disorders. Additionally, we discuss what stem cell therapy offers in specific acute and chronic lung disorders which includes respiratory distress syndrome (RDS), chronic obstructive pulmonary disease (COPD), asthma, fibrosis, bronchopulmonary dysplasia (BPD), and pulmonary hypertension.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdollahi A et al (2005) Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med 201:925–935
Abman SH, Matthay MA (2009) Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia: delivering the secretome. Am J Respir Crit Care Med 180:1039–1041
Abreu SC et al (2013) Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma. Respir Physiol Neurobiol 187:190–198
Admyre C et al (2008) Exosomes - nanovesicles with possible roles in allergic inflammation. Allergy 63:404–408
Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822
Ahn SY, Chang YS, Park WS (2015) Stem cell therapy for bronchopulmonary dysplasia: bench to bedside translation. J Korean Med Sci 30:509–513
Akram KM, Samad S, Spiteri MA, Forsyth NR (2013) Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms. Respir Res 14:9
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738
Antoniou KM et al (2010) Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in idiopathic pulmonary fibrosis (IPF). Respir Med 104:1535–1542
Antunes MA, Laffey JG, Pelosi P, Rocco PRM (2014) Mesenchymal stem cell trials for pulmonary diseases. J Cell Biochem 115:1023–1032
Anversa P, Kajstura J, Leri A, Loscalzo J (2011) Tissue-specific adult stem cells in the human lung. Nat Med 17:1038–1039
Anversa P, Perrella MA, Kourembanas S, Choi AMK, Loscalzo J (2012) Regenerative pulmonary medicine: potential and promise, pitfalls and challenges. Eur J Clin Invest 42:900–913
Archer SL, Weir EK, Wilkins MR (2010) Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 121:2045–2066
Aslam M et al (2009) Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med 180:1122–1130
Augello A et al (2005) Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol 35:1482–1490
Baber SR et al (2007) Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Heart Circ Physiol 292:H1120–H1128
Badylak SF, Weiss DJ, Caplan A, Macchiarini P (2012) Engineered whole organs and complex tissues. Lancet (London, England) 379:43–52
Baksh D, Boland GM, Tuan RS (2007) Cross-talk between Wnt signaling pathways in human mesenchymal stem cells leads to functional antagonism during osteogenic differentiation. J Cell Biochem 101:1109–1124
Barst RJ (2005) PDGF signaling in pulmonary arterial hypertension. J Clin Invest 115:2691–2694
Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T (2008) Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Cell Stem Cell 2:566–575
Berg T et al (2010) β-catenin regulates mesenchymal progenitor cell differentiation during hepatogenesis. J Surg Res 164:276–285
Bernardo ME, Locatelli F, Fibbe WE (2009) Mesenchymal stromal cells. Ann N Y Acad Sci 1176:101–117
Beyth S et al (2010) and induce T-cell unresponsiveness human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105:2214–2219
Bianco P, Robey PG, Simmons PJ (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2:313–319
Bieback K, Klüter H (2007) Mesenchymal stromal cells from umbilical cord blood. Curr Stem Cell Res Ther 2:310–323
Bitencourt CS et al (2011) Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis. Fibrogenesis Tissue Repair 4:3
Braza F et al (2016) Mesenchymal stem cells induce suppressive macrophages through phagocytosis in a mouse model of asthma. Stem Cells. doi:10.1002/stem.2344
Brewster CE et al (1990) Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 3:507–511
Budhiraja R, Tuder RM, Hassoun PM (2004) Endothelial dysfunction in pulmonary hypertension. Circulation 109:159–165
Calió ML et al (2014) Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model. Free Radic Biol Med 70:141–154
Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347
Cargnoni A et al (2009) Transplantation of allogeneic and xenogeneic placenta-derived cells reduces bleomycin-induced lung fibrosis. Cell Transplant 18:405–422
Chamberlain G, Fox J, Ashton B, Middleton J (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25:2739–2749
Chang YS et al (2011) Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats. Cell Transplant 20:1843–1854
Cho SW et al (2008) Differential effects of secreted frizzled-related proteins (sFRPs) on osteoblastic differentiation of mouse mesenchymal cells and apoptosis of osteoblasts. Biochem Biophys Res Commun 367:399–405
Churg A et al (2003) Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-alpha release. Am J Respir Crit Care Med 167:1083–1089
Corcione A et al (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107:367–372
Crisan M et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313
Cruz FF et al (2015) Systemic administration of human bone marrow-derived mesenchymal stromal cell extracellular vesicles ameliorates aspergillus hyphal extract-induced allergic airway inflammation in immunocompetent mice. Stem Cells Transl Med 4:1302–1316
Cubillo I, Mirones I, Mari L (2014) Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma. Allergy 69:730–740
Dazzi F, Marelli-Berg FM (2008) Mesenchymal stem cells for graft-versus-host disease: close encounters with T cells. Eur J Immunol 38:1479–1482
De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 44:1928–1942
De Boer J, Wang HJ, Van Blitterswijk C (2014) Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng 10:393–401
ARDS Definition Task Force et al (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307:2526–2533
Di Ianni M et al (2008) Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 36:309–318
Di Nicola M et al (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843
Dimmeler S, Losordo D, Williams AR, Hare JM (2011) Implications for Cardiac Disease. 016960:910–922
Doeing DC, Solway J (2013) Airway smooth muscle in the pathophysiology and treatment of asthma. J Appl Physiol 114:834–843
Dolgachev VA, Ullenbruch MR, Lukacs NW, Phan SH (2009) Role of stem cell factor and bone marrow-derived fibroblasts in airway remodeling. Am J Pathol 174:390–400
Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8:315–317
Etheridge SL, Spencer GJ, Heath DJ, Genever PG (2004) Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells. Stem Cells 22:849–860
Favre J, Terborg N, Horrevoets AJG (2013) The diverse identity of angiogenic monocytes. Eur J Clin Invest 43:100–107
Foronjy RF, Majka SM (2012) The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: understanding microenvironmental cues. Cells 1:874–885
Fredenburgh LE, Perrella MA, Mitsialis SA (2007) The role of heme oxygenase-1 in pulmonary disease. Am J Respir Cell Mol Biol 36:158–165
Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247
GarcÃa-Castro J et al (2008) Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool. J Cell Mol Med 12:2552–2565
Gazdhar A et al (2013) HGF expressing stem cells in usual interstitial pneumonia originate from the bone marrow and are antifibrotic. PLoS One 8:e65453
Ghofrani HA, Seeger W, Grimminger F (2005) Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 353:1412–1413
Giaid A, Saleh D (1995) Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333:214–221
Giaid A et al (1993) Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 328:1732–1739
Gizycki MJ, Adelroth E, Rogers AV, O’Byrne PM, Jeffery PK (1997) Myofibroblast involvement in the allergen-induced late response in mild atopic asthma. Am J Respir Cell Mol Biol 16:664–673
Glennie S, Soeiro I, Dyson PJ, Lam EW-F, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105:2821–2827
Goodwin M et al (2011) Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice. Stem Cells 29:1137–1148
Gronthos S et al (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 116:1827–1835
Guan X-J et al (2013) Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors. J Cell Biochem 114:323–335
Guo F et al (2008) CD28 controls differentiation of regulatory T cells from naive CD4 T cells. J Immunol 181(4):2285–2291
Gupta N et al (2007) Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 179:1855–1863
Gupta N et al (2012) Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax 67:533–539
Hanania NA (2008) Targeting airway inflammation in asthma: current and future therapies. Chest 133:989–998
Hansmann G et al (2012) Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ 2:170–181
Heldin CH, Westermark B (1999) Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79:1283–1316
Huh JW et al (2011) Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am J Physiol Lung Cell Mol Physiol 301:L255–L266
Humbert M et al (2004) Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43:13S–24S
Hung C et al (2013) Role of lung pericytes and resident fibroblasts in the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med 188:820–830
Igura K et al (2004) Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy 6:543–553
Islam MN et al (2012) Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med 18:759–765
Jiang Y et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49
Jin Z et al (2015) Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease. J Int Med Res 43:303–310
Jones EA et al (2002) Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 46:3349–3360
Jones EA et al (2004) Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum 50:817–827
Joo S-Y et al (2010) Mesenchymal stromal cells inhibit graft-versus-host disease of mice in a dose-dependent manner. Cytotherapy 12:361–370
Jun D et al (2011) The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation. Stem Cells 29:725–735
Jurasz P, Courtman D, Babaie S, Stewart DJ (2010) Role of apoptosis in pulmonary hypertension: from experimental models to clinical trials. Pharmacol Ther 126:1–8
Kajstura J et al (2011) Evidence for human lung stem cells. N Engl J Med 364:1795–1806
Kanazawa H, Yoshikawa J (2005) Elevated oxidative stress and reciprocal reduction of vascular endothelial growth factor levels with severity of COPD. Chest 128:3191–3197
Kanki-Horimoto S et al (2006) Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation 114:I181–I185
Keating A (2008) How do mesenchymal stromal cells suppress T cells? Cell Stem Cell 2:106–108
Kim N, Cho S-G (2013) Clinical applications of mesenchymal stem cells. Korean J Intern Med 28:387–402
Kim S-Y et al (2012) Mesenchymal stem cell-conditioned media recovers lung fibroblasts from cigarette smoke-induced damage. Am J Physiol Lung Cell Mol Physiol 302:L891–L908
Kinnaird T et al (2004) Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 94:678–685
Kirton JP, Crofts NJ, George SJ, Brennan K, Canfield AE (2007) Wnt/beta-catenin signaling stimulates chondrogenic and inhibits adipogenic differentiation of pericytes: potential relevance to vascular disease? Circ Res 101:581–589
Kolf CM, Cho E, Tuan RS (2007) Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 9:204
Kolios G, Moodley Y (2013) Introduction to stem cells and regenerative medicine. Respiration 85:3–10
Königshoff M et al (2009) WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. J Clin Invest 119:772–787
Kotton DN et al (2001) Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 128:5181–5188
Krampera M et al (2006) Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24:386–398
Kulterer B et al (2007) Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. BMC Genomics 8:70
Kunter U et al (2006) Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol 17:2202–2212
Lama VN et al (2007) Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin Invest 117:989–996
Lathrop MJ et al (2014) Mesenchymal stromal cells mediate Aspergillus hyphal extract-induced allergic airway inflammation by inhibition of the Th17 signaling pathway. Stem Cells Transl Med 3:194–205
Le Blanc K et al (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet (Lond) 371:1579–1586
Lee C et al (2012) Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation 126:2601–2611
Leyns L, Bouwmeester T, Kim SH, Piccolo S, De Robertis EM (1997) Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell 88:747–756
Li L et al (2009) Paracrine action mediate the antifibrotic effect of transplanted mesenchymal stem cells in a rat model of global heart failure. Mol Biol Rep 36:725–731
Li J, Li D, Liu X, Tang S, Wei F (2012) Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats. J Inflamm (Lond) 9:33
Liang J et al (2010) Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 69:1423–1429
Liang OD et al (2011) Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells 29:99–107
Lim J et al (2016) Priming with ceramide 1 phosphate promotes the therapeutic effect of mesenchymal stem / stromal cells on pulmonary artery hypertension. PubMed Commons 473:3–4
Ling L, Nurcombe V, Cool SM (2009) Wnt signaling controls the fate of mesenchymal stem cells. Gene 433:1–7
Liu A-R et al (2013) 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 228:1270–1283
Luan Y et al (2012) Implantation of mesenchymal stem cells improves right ventricular impairments caused by experimental pulmonary hypertension. Am J Med Sci 343:402–406
Macchiarini P et al (2008) Clinical transplantation of a tissue-engineered airway. Lancet (London, England) 372:2023–2030
Madec AM et al (2009) Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells. Diabetologia 52:1391–1399
Marigo I, Dazzi F (2011) The immunomodulatory properties of mesenchymal stem cells. Semin Immunopathol 33:593–602
Mariñas-Pardo L et al (2014) Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma. Allergy Eur J Allergy Clin Immunol 69:730–740
Martin J, Helm K, Ruegg P, Burnham E, Majka S (2008) Adult lung side population cells have mesenchymal stem cell potential. Cytotherapy 10:140–151
MartÃnez-González I et al (2013) Human mesenchymal stem cells overexpressing the IL-33 antagonist soluble IL-1 receptor-like-1 attenuate endotoxin-induced acute lung injury. Am J Respir Cell Mol Biol 49:552–562
McQualter JL, Yuen K, Williams B, Bertoncello I (2010) Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. Proc Natl Acad Sci U S A 107:1414–1419
Mei SHJ et al (2010) Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med 182:1047–1057
Meisel R et al (2004) Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 103:4619–4621
Minguell JJ, Erices A (2006) Mesenchymal stem cells and the treatment of cardiac disease. Exp Biol Med (Maywood) 231:39–49
Moeller A et al (2009) Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179:588–594
Moodley Y et al (2009) Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 175:303–313
Moodley Y et al (2010) Human amnion epithelial cell transplantation abrogates lung fibrosis and augments repair. Am J Respir Crit Care Med 182:643–651
Moorman JE et al (2007) National surveillance for asthma--United States, 1980–2004. MMWR Surveill Summ 56:1–54
Murphy DM, O’Byrne PM (2010) Recent advances in the pathophysiology of asthma. Chest 137:1417–1426
Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006) Mesenchymal stem cells inhibit generation and function of both CD34 + -derived and monocyte-derived dendritic cells. J Immunol 177:2080–2087
Németh K et al (2009) Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 15:42–49
Nichols JE, Niles JA, Cortiella J (2012) Production and utilization of acellular lung scaffolds in tissue engineering. J Cell Biochem 113:2185–2192
Nihlberg K et al (2006) Tissue fibrocytes in patients with mild asthma: a possible link to thickness of reticular basement membrane? Respir Res 7:50
Noble PW et al (2011) Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet (London, England) 377:1760–1769
Ogulur I et al (2014) Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma. Int Immunopharmacol 20:101–109
Ohnishi S, Sumiyoshi H, Kitamura S, Nagaya N (2007) Mesenchymal stem cells attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions. FEBS Lett 581:3961–3966
Ortiz LA et al (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100:8407–8411
Ortiz LA et al (2007) Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A 104:11002–11007
Parekkadan B, Milwid JM (2010) Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 12:87–117
Park J-A et al (2012) Tissue factor-bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo. J Allergy Clin Immunol 130:1375–1383
Parsons PE et al (2005) Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 33:1–6; discussion 230–232
Patel SA et al (2010) Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol 184:5885–5894
Petersen TH et al (2010) Tissue-engineered lungs for in vivo implantation. Science 329:538–541
Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11:1255–1265
Pittenger MF et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Pochampally RR, Smith JR, Ylostalo J, Prockop DJ (2004) Serum deprivation of human marrow stromal cells (hMSCs) selects for a subpopulation of early progenitor cells with enhanced expression of OCT-4 and other embryonic genes. Blood 103:1647–1652
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74
Prockop DJ, Oh JY (2009) Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther 20:14–20
Qayyum AA et al (2012) Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design. Regen Med 7:421–428
Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G (2006) Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 174:810–816
Raghu G et al (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824
Ramos-Barbón D et al (2010) T Cells localize with proliferating smooth muscle alpha-actin + cell compartments in asthma. Am J Respir Crit Care Med 182:317–324
Ratajczak MZ, Zuba-Surma EK, Machalinski B, Kucia M (2007) Bone-marrow-derived stem cells--our key to longevity? J Appl Genet 48:307–319
Rehman J et al (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109:1292–1298
Ren G et al (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2:141–150
Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850
Ribeiro-Paes JT et al (2011) Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema. Int J Chron Obstruct Pulmon Dis 6:63–71
Robinson DS (2010) The role of the T cell in asthma. J Allergy Clin Immunol 126:1081–91; quiz 1092–1093
Rochefort GY et al (2006) Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem Cells 24:2202–2208
Rogers I, Casper RF (2004) Umbilical cord blood stem cells. Best Pract Res Clin Obstet Gynaecol 18:893–908
Rojas M et al (2005) Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 33:145–152
Rubio L, Vera-Sempere FJ, Lopez-Guerrero JA, Padilla J, Moreno-Baylach MJ (2005) A risk model for non-small cell lung cancer using clinicopathological variables, angiogenesis and oncoprotein expression. Anticancer Res 25(1B):497–504
Sakao S, Tatsumi K, Voelkel NF (2009) Endothelial cells and pulmonary arterial hypertension: apoptosis, proliferation, interaction and transdifferentiation. Respir Res 10:95
Saunders R et al (2009) Fibrocyte localization to the airway smooth muscle is a feature of asthma. J Allergy Clin Immunol 123:376–384
Schermuly RT et al (2005) Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115:2811–2821
Schipani E, Kronenberg HM (2008) Adult mesenchymal stem cells. In: StemBook. The Stem Cell Research Community. doi:10.3824/stembook.1.38.1, http://www.stembook.org
Schmidt M, Sun G, Stacey MA, Mori L, Mattoli S (2003) Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J Immunol 171:380–389
Semënov MV et al (2001) Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol 11:951–961
Shigemura N et al (2006) Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema. Am J Transplant 6:2592–2600
Simonneau G et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62:D34–D41
Smith VC et al (2005) Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002. J Pediatr 146:469–473
Spees JL, Olson SD, Whitney MJ, Prockop DJ (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 103:1283–1288
Spees JL et al (2008) Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension. FASEB J 22:1226–1236
Stagg J, Pommey S, Eliopoulos N, Galipeau J (2006) Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood 107:2570–2577
Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M (2001) Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. J Bone Miner Res 16:1120–1129
Summer R, Fitzsimmons K, Dwyer D, Murphy J, Fine A (2007) Isolation of an adult mouse lung mesenchymal progenitor cell population. Am J Respir Cell Mol Biol 37:152–159
Takemiya K et al (2010) Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats. Basic Res Cardiol 105:409–417
Taniguchi H et al (2010) Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J 35:821–829
Thibeault DW, Mabry SM, Ekekezie II, Zhang X, Truog WE (2003) Collagen scaffolding during development and its deformation with chronic lung disease. Pediatrics 111:766–776
Tropea KA et al (2012) The promise of stem cells in bronchopulmonary dysplasia. Pediatrics 2:6
Trounson A, Thakar RG, Lomax G, Gibbons D (2011) Clinical trials for stem cell therapies. BMC Med 9:52
Tsai M-S, Lee J-L, Chang Y-J, Hwang S-M (2004) Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod 19:1450–1456
Tsutsumi S et al (2001) Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 288:413–419
Tuder RM et al (1999) Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159:1925–1932
Umar S et al (2009) Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension. Am J Physiol Heart Circ Physiol 297:H1606–H1616
Uren A et al (2000) Secreted frizzled-related protein-1 binds directly to Wingless and is a biphasic modulator of Wnt signaling. J Biol Chem 275:4374–4382
van Haaften T et al (2009) Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med 180:1131–1142
Veevers-Lowe J, Ball SG, Shuttleworth A, Kielty CM (2011) Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activation of PDGFR-β and potentiation of growth factor signals. J Cell Sci 124:1288–1300
Vosdoganes P, Lim R, Moss TJM, Wallace EM (2012) Cell therapy: a novel treatment approach for bronchopulmonary dysplasia. Pediatrics 130:727–737
Walker N et al (2011) Resident tissue-specific mesenchymal progenitor cells contribute to fibrogenesis in human lung allografts. Am J Pathol 178:2461–2469
Walsh MC et al (2006) Summary proceedings from the bronchopulmonary dysplasia group. Pediatrics 117:S52–S56
Wang S, Wilkes MC, Leof EB, Hirschberg R (2005) Imatinib mesylate blocks a non-Smad TGF-beta pathway and reduces renal fibrogenesis in vivo. FASEB J 19:1–11
Wang M, Crisostomo PR, Herring C, Meldrum KK, Meldrum DR (2006) Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol 291:R880–R884
Ware LB et al (2007) Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med 35:1821–1828
Waterman RS, Henkle SL, Betancourt AM (2012) Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. PLoS One 7:e45590
Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP (2013) A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 143:1590–1598
Weiss DJ et al (2014) An official American thoracic society workshop report : stem cells and cell therapies in lung biology and diseases. doi:10.1513/AnnalsATS.201502-086ST
Williams AR, Hare JM (2011) Mesenchymal stem cells: Biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 109:923–940
Wong AP et al (2007) Targeted cell replacement with bone marrow cells for airway epithelial regeneration. Am J Physiol Lung Cell Mol Physiol 293:L740–L752
Wu P-S, Egger B, Brand AH (2008) Asymmetric stem cell division: lessons from Drosophila. Semin Cell Dev Biol 19:283–293
Xu Y, Malladi P, Wagner DR, Longaker MT (2005) Adipose-derived mesenchymal cells as a potential cell source for skeletal regeneration. Curr Opin Mol Ther 7:300–305
Yang J, Jia Z (2014) Cell-based therapy in lung regenerative medicine. Regen Med Res 2:1–7
Yang J et al (2013) Activated alveolar epithelial cells initiate fibrosis through secretion of mesenchymal proteins. Am J Pathol 183:1559–1570
Zeng SLIN, Wang LIHUI, Li P, Wang WEI, Yang J (2015) Mesenchymal stem cells abrogate experimental asthma by altering dendritic cell function. 2511–2520. doi:10.3892/mmr.2015.3706
Zhao YD et al (2005) Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 96:442–450
Zhao X et al (2014) The toll-like receptor 3 ligand, poly(I:C), improves immunosuppressive function and therapeutic effect of mesenchymal stem cells on sepsis via inhibiting MiR-143. Stem Cells 32:521–533
Zhen G et al (2008) Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Front Biosci 13:3415–3422
Zhen G et al (2010) Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells. Cytotherapy 12:605–614
Zheng G et al (2014) Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells : a randomized, placebo-controlled pilot study. Respir Res 15:39
Zhu Y-G et al (2014) Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells 32:116–125
Zhu Z, Fang Z, Hu X, Zhou S (2015) MicroRNAs and mesenchymal stem cells : hope for pulmonary hypertension. 30:380–385
Zvaifler NJ et al (2000) Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2:477–488
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Sharma, K., Husain, S.Y., Das, P., Hussain, M., Syed, M.A. (2017). Regenerative Potential of Mesenchymal Stem Cells: Therapeutic Applications in Lung Disorders. In: Pham, P. (eds) Liver, Lung and Heart Regeneration. Stem Cells in Clinical Applications. Springer, Cham. https://doi.org/10.1007/978-3-319-46693-4_6
Download citation
DOI: https://doi.org/10.1007/978-3-319-46693-4_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-46692-7
Online ISBN: 978-3-319-46693-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)