Intratracheal administration of mesenchymal stem cells modulates tachykinin system, suppresses airway remodeling and reduces airway hyperresponsiveness in an animal model

PLoS ONE

Volumn 11, Issue 7, 2016, Pages

  Urbanek, Konrad ^a   De Angelis, Antonella ^a   Spaziano, Giuseppe ^a   Piegari, Elena ^a   Matteis, Maria ^a   Cappetta, Donato ^a   Esposito, Grazia ^a   Russo, Rosa ^a   Tartaglione, Gioia ^a   De Palma, Raffaele ^a   Rossi, Francesco ^a   D'Agostino, Bruno ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

GREEN FLUORESCENT PROTEIN; INDOLEAMINE 2,3 DIOXYGENASE; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 5; NEUROKININ 1 RECEPTOR; NEUROKININ 2 RECEPTOR; NEUROPEPTIDE; TACHYKININ; IL10 PROTEIN, MOUSE; OVALBUMIN;

AIRWAY REMODELING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTHMA; CELL DIFFERENTIATION; CELL FATE; CONTROLLED STUDY; FUNCTION TEST; GOBLET CELL; HISTOPATHOLOGY; HOMEOSTASIS; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; LUNG LAVAGE; MESENCHYMAL STEM CELL; MUSCLE MASS; NONHUMAN; PHENOTYPE; PROTEIN ANALYSIS; PROTEIN EXPRESSION; RESPIRATORY TRACT ALLERGY; SMOOTH MUSCLE; SMOOTH MUSCLE CELL; STEM CELL TRANSPLANTATION; TISSUE HOMEOSTASIS; UPREGULATION; ANIMAL; BAGG ALBINO MOUSE; BRONCHOALVEOLAR LAVAGE FLUID; CHEMICALLY INDUCED; CHEMISTRY; CYTOLOGY; ENDOTRACHEAL INTUBATION; GENE EXPRESSION; GENETICS; IMMUNOLOGY; LUNG; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMA CELL; METABOLISM; MOUSE; PATHOLOGY; REPORTER GENE; RESPIRATORY HYPERSENSITIVITY;

ANIMALS; BRONCHOALVEOLAR LAVAGE FLUID; GENE EXPRESSION; GENES, REPORTER; GREEN FLUORESCENT PROTEINS; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; INTERLEUKIN-10; INTERLEUKIN-13; INTERLEUKIN-4; INTERLEUKIN-5; INTUBATION, INTRATRACHEAL; LUNG; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; MICE; MICE, INBRED BALB C; OVALBUMIN; RECEPTORS, NEUROKININ-1; RECEPTORS, NEUROKININ-2; RESPIRATORY HYPERSENSITIVITY;

EID: 84979530340     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0158746     Document Type: Article

References (78)

1. http://www.who.int/mediacentre/factsheets/fs307/en/index.html
2. Pascual RM, Peters SP. Airway remodeling contributes to the progressive loss of lung function in asthma: an overview. J Allergy Clin Immunol 2005; 116:477-486. PMID: 16159612
3. Temelkovski J, Hogan S, Shepherd D, Foster P, Kumar R. An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen. Thorax 1998; 53:849-856. PMID: 10193371
4. Trevor JL, Deshane JS. Refractory asthma: mechanisms, targets, and therapy. Allergy 2014; 69:817-827. doi: 10.1111/all.12412 PMID: 24773466
5. Kotton DN, Morrisey EE. Lung regeneration: mechanisms, applications and emerging stem cell populations. Nat Med 2014; 20:822-832. doi: 10.1038/nm.3642 PMID: 25100528
6. Walters MS, Gomi K, Ashbridge B, Moore MA, Arbelaez V, Heldrich J, et al. Generation of a human airway epithelium derived basal cell line with multipotent differentiation capacity. Respir Res 2013; 14:135. doi: 10.1186/1465-9921-14-135 PMID: 24298994
7. Hackett TL, Shaheen F, Johnson A, Wadsworth S, Pechkovsky DV, Jacoby DB, et al. Characterization of side population cells from human airway epithelium. Stem Cells 2008; 26:2576-2585. doi: 10.1634/stemcells.2008-0171 PMID: 18653771
8. Reynolds SD, Malkinson AM. Clara cell: progenitor for the bronchiolar epithelium. Int J Biochem Cell Biol 2010; 42:1-4. doi: 10.1016/j.biocel.2009.09.002 PMID: 19747565
9. Shiomi T, Sklepkiewicz P, Bodine PV, D'Armiento JM. Maintenance of the bronchial alveolar stem cells in an undifferentiated state by secreted frizzled-related protein 1. FASEB J 2014; 28:5242-5249. doi: 10.1096/fj.13-242735 PMID: 25212222
10. Barkauskas CE, Cronce MJ, Rackley CR, Bowie EJ, Keene DR, Stripp BR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 2013; 123:3025-3036. doi: 10.1172/JCI68782 PMID: 23921127
11. Hoffman AM, Paxson JA, Mazan MR, Davis AM, Tyagi S, Murthy S, Ingenito EP. Lung-derived mesenchymal stromal cell post-transplantation survival, persistence, paracrine expression, and repair of elastase-injured lung. Stem Cells Dev 2011; 20:1779-1792. doi: 10.1089/scd.2011.0105 PMID: 21585237
12. Weiss DJ, Bertoncello I, Borok Z, Kim C, Panoskaltsis-Mortari A, Reynolds S, et al. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc 2011; 8:223-272. doi: 10.1513/pats.201012-071DW PMID: 21653527
13. Lau AN, Goodwin M, Kim CF, Weiss DJ. Stem cells and regenerative medicine in lung biology and diseases. Mol Ther 2012; 20:1116-1130. doi: 10.1038/mt.2012.37 PMID: 22395528
14. Sabatini F, Petecchia L, Tavian M, Jodon de Villeroché V, Rossi GA, Brouty-Boyé D. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest 2005; 85:962-971. PMID: 15924148
15. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147. PMID: 10102814
16. Spees JL, Olson SD, Ylostalo J, Lynch PJ, Smith J, Perry A. Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc Natl Acad Sci USA 2003; 100:2397-2402. PMID: 12606728
17. Visweswaran M, Pohl S, Arfuso F, Newsholme P, Dilley R, Pervaiz S, Dharmarajan A. Multi-lineage differentiation of mesenchymal stem cells - To Wnt, or not Wnt. Int J Biochem Cell Biol 2015; 68:139-147. doi: 10.1016/j.biocel.2015.09.008 PMID: 26410622
18. Sinclair K, Yerkovich ST, Chambers DC. Mesenchymal stem cells and the lung. Respirology 2013; 18:397-411. doi: 10.1111/resp.12050 PMID: 23316733
19. D'Agostino B, Sullo N, Siniscalco D, De Angelis A, Rossi F. Mesenchymal stem cell therapy for the treatment of chronic obstructive pulmonary disease. Expert Opin Biol Ther 2010; 10:681-687. doi: 10.1517/14712591003610614 PMID: 20384521
20. Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003; 101:3722-3729. PMID: 12506037
21. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107:367-372. PMID: 16141348
22. Rasmusson I, Ringden O, Sundberg B, Le Blanc K. Mesenchymal stem cells inhibxit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76:1208-1213. PMID: 14578755
23. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N. Human mesenchymal stem cells inhibit differentiation and function of monocytederived dendritic cells. Blood 2005; 105:4120-4126. PMID: 15692068
24. Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, et al. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med 2012; 18:759-765. doi: 10.1038/nm.2736 PMID: 22504485
25. Zhu YG, Feng XM, Abbott J, Fang XH, Hao Q, Monsel A, et al. Human mesenchymal stem cell microvesicles for treatment of escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells 2014; 32:116-125. doi: 10.1002/stem.1504 PMID: 23939814
26. Guan XJ, Song L, Han FF, Cui ZL, 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. doi: 10.1002/jcb.24377 PMID: 22949406
27. 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. doi: 10.3109/14653241003745888 PMID: 20429787
28. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007; 179:1855-1863. PMID: 17641052
29. Ionescu L, Byrne RN, van Haaften T, Vadivel A, Alphonse RS, Rey-Parra GJ, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol 2012; 303:967-977.
30. van Haaften T, Byrne R, Bonnet S, Rochefort GY, Akabutu J, Bouchentouf M, et al. Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med 2009; 180:1131-1142. doi: 10.1164/rccm.200902-0179OC PMID: 19713449
31. Kanki-Horimoto S, Horimoto H, Mieno S, Kishida K, Watanabe F, Furuya E, Katsumata T. Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation 2006; 114:I181-I185. PMID: 16820570
32. Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 2009; 175:303-313. doi: 10.2353/ajpath.2009.080629 PMID: 19497992
33. 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 Natl Acad Sci USA 2003; 100:8407-8411. PMID: 12815096
34. Raza K, Larsen T, Samaratunga N, Price AP, Meyer C, Matson A, et al. MSC therapy attenuates obliterative bronchiolitis after murine bone marrow transplant. PLoS One 2014; 9:e109034. doi: 10.1371/journal.pone.0109034 PMID: 25272285
35. Duong KM, Arikkatt J, Ullah MA, Lynch JP, Zhang V, Atkinson K, et al. Immunomodulation of Airway Epithelium Cell Activation by Mesenchymal Stromal Cells Ameliorates House Dust Mite-Induced Airway Inflammation in Mice. Am J Respir Cell Mol Biol 2015; 53:615-624. doi: 10.1165/rcmb.2014-0431OC PMID: 25789608
36. Firinci F, Karaman M, Baran Y, Bagriyanik A, Ayyildiz ZA, Kiray M, et al. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma. Int Immunopharmacol 2011; 11:1120-1126. doi: 10.1016/j.intimp.2011.03.009 PMID: 21439399
37. Nemeth K, Keane-Myers A, Brown JM, Metcalfe DD, Gorham JD, Bundoc VG, et al. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci USA 2010; 107:5652-5657. doi: 10.1073/pnas.0910720107 PMID: 20231466
38. 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. doi: 10.1152/ajplung.00182.2009 PMID: 20817776
39. Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant 2015; in press.
40. Phinney DG, Kopen G, Isaacson RL, Prockop DJ. Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem 1999; 72:570-585. PMID: 10022616
41. Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, et al. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nat Med 2011; 17:1594-1601. doi: 10.1038/nm.2542 PMID: 22101767
42. Song L, Liu D, Wu C, Wu S, Yang J, Ren F, Li Y. Antibody to mCLCA3 suppresses symptoms in a mouse model of asthma. PLoS One 2013; 8:e82367. doi: 10.1371/journal.pone.0082367 PMID: 24349268
43. Garbacki N, Di Valentin E, Huynh-Thu VA, Geurts P, Irrthum A, Crahay C, et al. MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. PLoS One 2011; 6: e16509. doi: 10.1371/journal.pone.0016509 PMID: 21305051
44. Sullo N, Roviezzo F, Matteis M, Ianaro A, Calò G, Guerrini R, et al. Nociceptin/orphanin FQ receptor activation decreases the airway hyperresponsiveness induced by allergen in sensitized mice. Am J Physiol Lung Cell Mol Physiol 2013; 304:657-664.
45. Vignali DA. Multiplexed particle-based flow cytometric assays. J Immunol Methods 2000; 243:243-255. PMID: 10986418
46. Crescenzi E, Pacifico F, Lavorgna A, De Palma R, D'Aiuto E, Palumbo G, et al. NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells. Oncogene 2011; 30:2707-2717. doi: 10.1038/onc.2011.1 PMID: 21278794
47. James AL, Hogg JC, Dunn LA, Paré PD. The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening. Am Rev Respir Dis 1988; 138:136-139. PMID: 3202392
48. De Angelis A, Piegari E, Cappetta D, Marino L, Filippelli A, Berrino L, et al. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation 2010; 121:276-292. doi: 10.1161/CIRCULATIONAHA.109.895771 PMID: 20038740
49. Cohen L, E X, Tarsi J, Ramkumar T, Horiuchi TK, Cochran R, DeMartino S, Schechtman KB, Hussain I, Holtzman MJ, Castro M; NHLBI Severe Asthma Research Program (SARP). Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med 2007; 176:138-145. PMID: 17463414
50. Mathias LJ, Khong SM, Spyroglou L, Payne NL, Siatskas C, Thorburn AN, et al. Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells. J Immunol 2013; 191:5914-5924. doi: 10.4049/jimmunol.1300667 PMID: 24249728
51. Groneberg DA, Quarcoo D, Frossard N, Fischer A. Neurogenic mechanisms in bronchial inflammatory diseases. Allergy 2004; 59:1139-1152. PMID: 15461593
52. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 2013; 13:392-402. doi: 10.1016/j.stem.2013.09.006 PMID: 24094322
53. Sun YQ, Deng MX, He J, Zeng QX, Wen W, Wong DS, et al. Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice. Stem Cells 2012; 30:2692-2699. doi: 10.1002/stem.1241 PMID: 22987325
54. Duong KM, Arikkatt J, Ullah MA, Lynch JP, Zhang V, Atkinson K, et al. Immunomodulation of Airway Epithelium Cell Activation by Mesenchymal Stromal Cells Ameliorates House Dust Mite-Induced Airway Inflammation in Mice. Am J Respir Cell Mol Biol 2015; 53:615-624. doi: 10.1165/rcmb.2014-0431OC PMID: 25789608
55. Royce SG, Shen M, Patel KP, Huuskes BM, Ricardo SD, Samuel CS. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease. Stem Cell Res 2015; 15:495-505. doi: 10.1016/j.scr.2015.09.007 PMID: 26426509
56. Abreu SC, Antunes MA, de Castro JC, de Oliveira MV, Bandeira E, Ornellas DS, et al. Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma. Respir Physiol Neurobiol 2013; 187:190-198. doi: 10.1016/j.resp.2013.03.014 PMID: 23548824
57. Ortiz LA, Treil MD, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. Interleukin 1 receptor antagonist mediates the anti-inflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA 2007; 104:11002-11007. PMID: 17569781
58. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147:3815-3822. PMID: 1940369
59. Lynch EL, Little FF, Wilson KC, Center DM, Cruikshank WW. Immunomodulatory cytokines in asthmatic inflammation. Cytokine Growth Factor Rev 2003; 14:489-502. PMID: 14563351
60. Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 2013; 34:137-143. doi: 10.1016/j.it.2012.10.001 PMID: 23103127
61. Raicevic G, Rouas R, Najar M, Stordeur P, Boufker HI, Bron D, et al. Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells. Hum Immunol 2010; 71:235-244. doi: 10.1016/j.humimm.2009.12.005 PMID: 20034529
62. Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, Yarmush ML. Mesenchymal stem cells: Mechanisms of immunomodulation and homing. Cell Transplant 2010; 19:667-679. doi: 10.3727/096368910X508762 PMID: 20525442
63. D'Agostino B, Advenier C, de Palma R, Gallelli L, Marrocco G, Abbate GF, Rossi F. The involvement of sensory neuropeptides in airway hyper-responsiveness in rabbits sensitized and challenged to Parietaria judaica. Clin Exp Allergy 2002; 32:472-479. Available: http://www.ncbi.nlm.nih.gov/pubmed/11940080
64. Gallelli L, D'Agostino B, Marrocco G, De Rosa G, Filippelli W, Rossi F, Advenier C. Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal instillation in the rabbit. Life Sci 2003; 72:1135-1142.
65. Ichinose M, Nakajima N, Takahashi T, Yamauchi H, Inoue H, Takishima T. Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist. Lancet 1992; 340:1248-1251. PMID: 1359319
66. Fahy JV, Wong HH, Geppetti P, Reis JM, Harris SC, Maclean DB, et al. Effect of an NK1 receptor antagonist (CP-99,994) on hypertonic saline-induced bronchoconstriction and cough in male asthmatic subjects. Am J Respir Crit Care Med 1995; 152:879-884. PMID: 7663799
67. Ichinose M, Miura M, Yamauchi H, Kageyama N, Tomaki M, Oyake T, et al. A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients. Am J Respir Crit Care Med 1996; 153:936-941. PMID: 8630576
68. Kraneveld AD, Nijkamp FP. Tachykinins and neuro-immune interactions in asthma. Int Immunopharmacol 2001; 1:1629-1650. PMID: 11562057
69. Vignola AM, Kips J, Bousquet J. Tissue remodeling as a feature of persistent asthma. J Allergy Clin Immunol 2000; 105:1041-1053. PMID: 10856134
70. Kobayashi M, Ashino S, Shiohama Y, Wakita D, Kitamura H, Nishimura T. IFN-γ elevates airway hyper-responsiveness via up-regulation of neurokinin A/neurokinin-2 receptor signaling in a severe asthma model. Eur J Immunol 2012; 42:393-402. doi: 10.1002/eji.201141845 PMID: 22105467
71. Bai TR, Zhou D, Weir T, Walker B, Hegele R, Hayashi S, et al. Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases. Am J Physiol 1995; 269:L309-L317. PMID: 7573463
72. Joos GF, Germonpré PR, Pauwels RA. Role of tachykinins in asthma. Allergy 2000; 55:321-337. PMID: 10782516
73. Ramalho R, Soares R, Couto N, Moreira A. Tachykinin receptors antagonism for asthma: a systematic review. BMC Pulm Med 2011; 11:41. doi: 10.1186/1471-2466-11-41 PMID: 21810226
74. Oslund KL, Hyde DM, Putney LF, Alfaro MF, Walby WF, Tyler NK, Schelegle ES. Activation of calcitonin gene-related peptide receptor during ozone inhalation contributes to airway epithelial injury and repair. Toxicol Pathol 2009; 37:805-813. doi: 10.1177/0192623309345691 PMID: 19700657
75. Guan CX, Zhang M, Qin XQ, Cui YR, Luo ZQ, Bai HB, Fang X. Vasoactive intestinal peptide enhances wound healing and proliferation of human bronchial epithelial cells. Peptides 2006; 27:3107-3114. PMID: 16965837
76. Burian B, Ortner A, Prassl R, Zimmer A, Mosgoeller W. Clinical potential of VIP by modified pharmacokinetics and delivery mechanisms. Endocr Metab Immune Disord Drug Targets 2012; 12:344-350. PMID: 23094831
77. Yao Y, Huang J, Geng Y, Qian H, Wang F, Liu X, et al. Paracrine action of mesenchymal stem cells revealed by single cell gene profiling in infarcted murine hearts. PLoS One 2015; 10:e0129164. doi: 10.1371/journal.pone.0129164 PMID: 26043119
78. Goodwin M, Sueblinvong V, Eisenhauer P, Ziats NP, LeClair L, Poynter ME, et al. Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice. Stem Cells 2011; 29:1137-1148. doi: 10.1002/stem.656 PMID: 21544902