title: Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.
abstract: Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma.
authors.affiliation: Dept. of Pediatrics, Case Western Reserve Univ., Cleveland, OH 44106-4948, USA. tracey.bonfield@case.edu
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Bonfield
authors.forename: Mary
authors.initials: M
authors.lastname: Koloze
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lennon
authors.forename: Brandon
authors.initials: B
authors.lastname: Zuchowski
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Yang
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Caplan
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002648:Child; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D009569:Nitric Oxide; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin
references.citation: Arthritis Res Ther. 2007;9(1):301
references.pmid: 17284303
references.citation: Regen Med. 2007 Sep;2(5):817-29
references.pmid: 17907933
references.citation: J Intern Med. 2007 Nov;262(5):509-25
references.pmid: 17949362
references.citation: Circulation. 2005 Jul 12;112(2):214-23
references.pmid: 15998673
references.citation: FASEB J. 2007 Oct;21(12):3197-207
references.pmid: 17496162
references.citation: Am J Pathol. 2002 Aug;161(2):491-8
references.pmid: 12163374
references.citation: Nat Rev Drug Discov. 2004 Oct;3(10):831-44
references.pmid: 15459674
references.citation: J Immunol. 2008 Sep 15;181(6):4389-96
references.pmid: 18768898
references.citation: Cytotherapy. 2006;8(4):315-7
references.pmid: 16923606
references.citation: J Leukoc Biol. 2004 Feb;75(2):163-89
references.pmid: 14525967
references.citation: Cells Tissues Organs. 2001;169(1):12-20
references.pmid: 11340257
references.citation: Clin Diagn Lab Immunol. 2005 Jul;12(7):821-4
references.pmid: 16002629
references.citation: Cell Immunol. 2002 Oct;219(2):92-7
references.pmid: 12576027
references.citation: Regen Med. 2006 Jul;1(4):497-509
references.pmid: 17465844
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):229-30
references.pmid: 18786406
references.citation: J Bone Miner Res. 1999 May;14(5):700-9
references.pmid: 10320518
references.citation: Am J Respir Crit Care Med. 1999 Dec;160(6):2040-7
references.pmid: 10588626
references.citation: Am J Respir Crit Care Med. 1995 Aug;152(2):800-3
references.pmid: 7633745
references.citation: Adv Exp Med Biol. 2006;585:49-64
references.pmid: 17120776
references.citation: Curr Opin Allergy Clin Immunol. 2005 Apr;5(2):161-6
references.pmid: 15764907
references.citation: Exp Hematol. 2000 Aug;28(8):875-84
references.pmid: 10989188
references.citation: Stem Cells. 2007 Nov;25(11):2739-49
references.pmid: 17656645
references.citation: J Pediatr. 1997 Sep;131(3):381-5
references.pmid: 9329413
references.citation: Proc Am Thorac Soc. 2008 Aug 15;5(6):711-6
references.pmid: 18684723
references.citation: Exp Hematol. 2006 Nov;34(11):1604-5
references.pmid: 17046583
references.citation: J Immunol. 2008 Jul 1;181(1):235-42
references.pmid: 18566389
references.citation: Cell Mol Biol (Noisy-le-grand). 2003 Sep;49(6):875-84
references.pmid: 14656045
references.citation: J Clin Invest. 2003 Feb;111(3):291-7
references.pmid: 12569150
references.citation: Ann Allergy Asthma Immunol. 2003 Jan;90(1 Suppl 1):1-40
references.pmid: 12542071
references.citation: Cytokine Growth Factor Rev. 2003 Dec;14(6):489-502
references.pmid: 14563351
references.citation: J Allergy Clin Immunol. 2006 Jan;117(1):111-8
references.pmid: 16387593
references.citation: BioDrugs. 2004;18(4):211-23
references.pmid: 15244499
references.citation: Connect Tissue Res. 1996;35(1-4):93-9
references.pmid: 9084647
references.citation: Lancet. 2008 May 10;371(9624):1579-86
references.pmid: 18468541
references.citation: Monaldi Arch Chest Dis. 2006 Mar;65(1):47-51
references.pmid: 16700195
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):301-13
references.pmid: 18786417
references.citation: Annu Rev Immunol. 2004;22:789-815
references.pmid: 15032597
references.citation: Curr Opin Allergy Clin Immunol. 2001 Dec;1(6):555-60
references.pmid: 11964741
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8407-11
references.pmid: 12815096
references.citation: Int J Cardiol. 2004 Jun;95 Suppl 1:S23-5
references.pmid: 15336840
references.citation: Methods Cell Biol. 2008;86:295-309
references.pmid: 18442653
references.citation: J Neurol Sci. 2008 Nov 15;274(1-2):68-75
references.pmid: 18789804
references.citation: Exp Toxicol Pathol. 2006 Jun;57 Suppl 2:3-4
references.pmid: 16584873
references.citation: Stem Cells. 2008 Sep;26(9):2287-99
references.pmid: 18566331
references.citation: Gene Ther. 2008 Jan;15(2):109-16
references.pmid: 17989700
references.citation: Trends Mol Med. 2001 Jun;7(6):259-64
references.pmid: 11378515
references.citation: Nat Med. 1999 Mar;5(3):309-13
references.pmid: 10086387
references.citation: Curr Opin Lipidol. 2007 Dec;18(6):645-9
references.pmid: 17993810
references.citation: J Pathol. 2009 Jan;217(2):318-24
references.pmid: 19023885
references.citation: J Cell Biochem. 2006 Aug 1;98(5):1076-84
references.pmid: 16619257