Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis

Journal of Clinical Investigation

Volumn 125, Issue 9, 2015, Pages 3606-3618

  Manieri, Nicholas A ^a   Mack, Madison R ^a   Himmelrich, Molly D ^a   Worthley, Daniel L ^b,c   Hanson, Elaine M ^d   Eckmann, Lars ^d   Wang, Timothy C ^b   Stappenbeck, Thaddeus S ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b New York Presbyterian Morgan Stanley Children's Hospital   (United States)

^c UNIVERSITY OF ADELAIDE   (Australia)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; ILOPROST; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; PLERIXAFOR; PROSTAGLANDIN E2; SHORT HAIRPIN RNA; TIVOZANIB; VASCULOTROPIN; PROSTACYCLIN; VASCULAR ENDOTHELIAL GROWTH FACTOR A, MOUSE; VASCULOTROPIN A;

ADULT; ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DEATH; CELL PROLIFERATION; CELL STIMULATION; COLON BIOPSY; COLON MUCOSA; COLONIC MUSCLE; COMPARATIVE STUDY; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; HYPOXEMIA; HYPOXIA; INTESTINE WALL; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MOUSE; MUSCLE NECROSIS; NONHUMAN; PENETRATING ULCER; PHENOTYPE; PRIORITY JOURNAL; TISSUE REGENERATION; ULCER; ULCER HEALING; ULCEROGENESIS; ALLOGRAFT; ANIMAL; COLON; GENETICS; INJURIES; INTESTINE MUCOSA; KNOCKOUT MOUSE; METABOLISM; PATHOLOGY; WOUND HEALING; WOUNDS AND INJURIES;

ALLOGRAFTS; ANIMALS; COLON; EPOPROSTENOL; INTESTINAL MUCOSA; MESENCHYMAL STEM CELL TRANSPLANTATION; MICE; MICE, KNOCKOUT; NEOVASCULARIZATION, PHYSIOLOGIC; VASCULAR ENDOTHELIAL GROWTH FACTOR A; WOUND HEALING; WOUNDS AND INJURIES;

EID: 84941710464     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI81423     Document Type: Article

References (58)

1. Almeida-Porada G, Soland M, Boura J, Porada CD. Regenerative medicine: prospects for the treatment of inflammatory bowel disease. Regen Med. 2013;8 (5) :631-644.
2. Voswinkel J, et al. Use of mesenchymal stem cells (MSC) in chronic inflammatory fistulizing and fibrotic diseases: A comprehensive review. Clin Rev Allergy Immunol. 2013;45 (2) :180-192.
3. Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011;6:457-478.
4. Manieri NA, Stappenbeck TS. Mesenchymal stem cell therapy of intestinal disease: Are their effects systemic or localized? Curr Opin Gastroenterol. 2011;27 (2) :119-124.
5. Fischer UM, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: The pulmonary first-pass effect. Stem Cells Dev. 2009;18 (5) :683-692.
6. Zaher W, Harkness L, Jafari A, Kassem M. An update of human mesenchymal stem cell biology and their clinical uses. Arch Toxicol. 2014;88 (5) :1069-1082.
7. Glenn JD, Whartenby KA. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy. World J Stem Cells. 2014;6 (5) :526-539.
8. Leoni G, et al. Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair. J Clin Invest. 2013;123 (1) :443-454.
9. Normand S, et al. Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury. Proc Natl Acad Sci U S A. 2011;108 (23) :9601-9606.
10. Pickert G, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med. 2009;206 (7) :1465-1472.
11. Seno H, Miyoshi H, Brown SL, Geske MJ, Colonna M, Stappenbeck TS. Efficient colonic mucosal wound repair requires Trem2 signaling. Proc Natl Acad Sci U S A. 2009;106 (1) :256-261.
12. Miyoshi H, Ajima R, Luo CT, Yamaguchi TP, Stappenbeck TS. Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury. Science. 2012;338 (6103) :108-113.
13. Lee SJ, Leoni G, Neumann PA, Chun J, Nusrat A, Yun CC. Distinct phospholipase C-beta isozymes mediate lysophosphatidic acid receptor 1 effects on intestinal epithelial homeostasis and wound closure. Mol Cell Biol. 2013;33 (10) :2016-2028.
14. Manieri NA, Drylewicz MR, Miyoshi H, Stappenbeck TS. Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice. Gastroenterology. 2012;143 (1) :110-121 e110.
15. Bataille F, et al. Morphological characterisation of Crohns disease fistulae. Gut. 2004;53 (9) :1314-1321.
16. Molendijk I, Peeters KC, Baeten CI, Veenendaal RA, van der Meulen-de Jong AE. Improving the outcome of fistulising Crohns disease. Best Pract Res Clin Gastroenterol. 2014;28 (3) :505-518.
17. Ballinger A. Adverse effects of nonsteroidal anti-inflammatory drugs on the colon. Curr Gastroenterol Rep. 2008;10 (5) :485-489.
18. Bjarnason I. Gastrointestinal safety of NSAIDs and over-The-counter analgesics. Int J Clin Pract. 2013; (178) :37-42.
19. Wang D, Mann JR, DuBois RN. The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology. 2005;128 (5) :1445-1461.
20. Langman MJ, Morgan L, Worrall A. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage. Br Med J (Clin Res Ed) . 1985;290:347-349.
21. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15 (suppl 3) :S3.
22. Tarnawski A, Szabo IL, Husain SS, Soreghan B. Regeneration of gastric mucosa during ulcer healing is triggered by growth factors and signal transduction pathways. J Physiol Paris. 2001;95 (1-6) :337-344.
23. Murata T, et al. Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Nature. 1997;388 (6643) :678-682.
24. Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. A global double-fluorescent Cre reporter mouse. Genesis. 2007;45 (9) :593-605.
25. Masferrer JL, et al. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci U S A. 1994;91 (8) :3228-3232.
26. Nauta TD, van Hinsbergh VW, Koolwijk P. Hypoxic signaling during tissue repair and regenerative medicine. Int J Mol Sci. 2014;15 (11) :19791-19815.
27. Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114 (8) :1098-1106.
28. Koch CJ. Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. Methods Enzymol. 2002;352:3-31.
29. Ferrara N, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380 (6573) :439-442.
30. Ben-Av P, Crofford LJ, Wilder RL, Hla T. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: A potential mechanism for inflammatory angiogenesis. FEBS Lett. 1995;372 (1) :83-87.
31. De Luca A, Normanno N. Tivozanib, a pan-VEGFR tyrosine kinase inhibitor for the potential treatment of solid tumors. IDrugs. 2010;13 (9) :636-645.
32. Sun L, et al. Type I interferons link viral infection to enhanced epithelial turnover and repair. Cell Host Microbe. 2015;17 (1) :85-97.
33. Watanabe S, et al. Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors. J Gastroenterol. 2014;49 (2) :270-282.
34. Walker MR, Brown SL, Riehl TE, Stenson WF, Stappenbeck TS. Growth factor regulation of prostaglandin-endoperoxide synthase 2 (Ptgs2) expression in colonic mesenchymal stem cells. J Biol Chem. 2010;285 (7) :5026-5039.
35. Lee RH, et al. 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 (1) :54-63.
36. Eppler SM, et al. A target-mediated model to describe the pharmacokinetics and hemodynamic effects of recombinant human vascular endothelial growth factor in humans. Clin Pharmacol Ther. 2002;72 (1) :20-32.
37. Wu Y, Zhao RC. The role of chemokines in mesenchymal stem cell homing to myocardium. Stem Cell Rev. 2012;8 (1) :243-250.
38. Marquez-Curtis LA, Janowska-Wieczorek A. Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis. Biomed Res Int. 2013;2013:561098.
39. Hummel S, Van Aken H, Zarbock A. Inhibitors of CXC chemokine receptor type 4: putative therapeutic approaches in inflammatory diseases. Curr Opin Hematol. 2014;21 (1) :29-36.
40. Voswinkel J, Francois S, Gorin NC, Chapel A. Gastro-intestinal autoimmunity: preclinical experiences and successful therapy of fistulizing bowel diseases and gut Graft versus host disease by mesenchymal stromal cells. Immunol Res. 2013;56 (2-3) :241-248.
41. Present DH. Crohns fistula: current concepts in management. Gastroenterology. 2003;124 (6) :1629-1635.
42. Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohns fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48 (7) :1416-1423.
43. Garcia-Olmo D, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: A phase II clinical trial. Dis Colon Rectum. 2009;52 (1) :79-86.
44. Martinez-Montiel Mdel P, Gomez-Gomez GJ, Flores AI. Therapy with stem cells in inflammatory bowel disease. World J Gastroenterol. 2014;20 (5) :1211-1227.
45. Kang S, Roh YJ, Kim IB. Antiangiogenic effects of tivozanib, an oral VEGF receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization in mice. Exp Eye Res. 2013;112:125-133.
46. Sliesoraitis S, Tawfik B. Bevacizumab-induced bowel perforation. J Am Osteopath Assoc. 2011;111 (7) :437-441.
47. Koutroubakis IE, Tsiolakidou G, Karmiris K, Kouroumalis EA. Role of angiogenesis in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12 (6) :515-523.
48. Tanaka K, Sano K, Kobayashi M, Katsumura K, Ikeda T, Abe M. Demonstration of downregulation of α-smooth muscle actin in interferon-γ-Treated myofibroblast by a novel cell-capture enzyme immunoassay. Int Immunopharmacol. 2001;1 (4) :769-775.
49. Sandbo N, Taurin S, Yau DM, Kregel S, Mitchell R, Dulin NO. Downregulation of smooth muscle alpha-Actin expression by bacterial lipopolysaccharide. Cardiovasc Res. 2007;74 (2) :262-269.
50. Takeuchi K. Prophylactic effects of prostaglandin E on NSAID-induced enteropathy-role of EP4 receptors in its protective and healing-promoting effects. Curr Opin Pharmacol. 2014;19C:38-45.
51. Gately S, Li WW. Multiple roles of COX-2 in tumor angiogenesis: A target for antiangiogenic therapy. Semin Oncol. 2004;31 (2 suppl 7) :2-11.
52. Wang J, et al. VEGF expression is augmented by hypoxiainduced PGIS in human fibroblasts. Int J Oncol. 2013;43 (3) :746-754.
53. Park DW, et al. Activation of toll-like receptor 4 modulates vascular endothelial growth factor synthesis through prostacyclin-IP signaling. Biochem Biophys Res Commun. 2007;362 (4) :1090-1095.
54. Whittle BJ, Silverstein AM, Mottola DM, Clapp LH. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: Treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012;84 (1) :68-75.
55. Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997;122 (2) :217-224.
56. Abramovitz M, et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta. 2000;1483 (2) :285-293.
57. Worthley DL, et al. Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell. 2015;160 (1-2) :269-284.
58. Morham SG, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell. 1995;83 (3) :473-482.