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Stem Cells International
Volume 2014 (2014), Article ID 340257, 26 pages
http://dx.doi.org/10.1155/2014/340257
Review Article

Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough

Radioprotection and Human Health Division, Institute of Radioprotection and Nuclear Safety, PRP-HOM/SRBE/LR2I, 92260 Fontenay-aux-Roses, France

Received 28 March 2014; Revised 5 June 2014; Accepted 5 June 2014; Published 14 July 2014

Academic Editor: Katherine Athayde Teixeira de Carvalho

Copyright © 2014 Benoît Usunier et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. V. Kumar, A. K. Abbas, and N. Fausto, “Tissue renewal and repair: regeneration, healing, and fibrosis,” in Pathologic Basis of Disease, V. K. A. K. Abbas and N. Fausto, Eds., Elsevier Saunders, Philadelphia, Pa, USA, 2005. View at Google Scholar
  2. T. A. Wynn, “Cellular and molecular mechanisms of fibrosis,” Journal of Pathology, vol. 214, no. 2, pp. 199–210, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Chapel, S. Francois, L. Douay, M. Benderitter, and J. Voswinkel, “New insights for pelvic radiation disease treatment: multipotent stromal cell is a promise mainstay treatment for the restoration of abdominopelvic severe chronic damages induced by radiotherapy,” World Journal of Stem Cells, vol. 5, no. 4, pp. 106–111, 2013. View at Google Scholar
  4. J. Voswinkel, S. Francois, N. Gorin, and A. Chapel, “Gastro-intestinal autoimmunity: Preclinical experiences and successful therapy of fistulizing bowel diseases and gut Graft versus host disease by mesenchymal stromal cells,” Immunologic Research, vol. 56, no. 2-3, pp. 241–248, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. S. C. Schwarz and J. Schwarz, “Translation of stem cell therapy for neurological diseases,” Translational Research, vol. 156, no. 3, pp. 155–160, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. T. A. Wynn and T. R. Ramalingam, “Mechanisms of fibrosis: therapeutic translation for fibrotic disease,” Nature Medicine, vol. 18, no. 7, pp. 1028–1040, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Gabbiani, “The biology of the myofibroblast,” Kidney International, vol. 41, no. 3, pp. 530–532, 1992. View at Publisher · View at Google Scholar · View at Scopus
  8. T. A. Wynn, “Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases,” Journal of Clinical Investigation, vol. 117, no. 3, pp. 524–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. Q. Yu and I. Stamenkovic, “Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis,” Genes and Development, vol. 14, no. 2, pp. 163–176, 2000. View at Google Scholar · View at Scopus
  10. M. H. Barcellos-Hoff and T. A. Dix, “Redox-mediated activation of latent transforming growth factor-β1,” Molecular Endocrinology, vol. 10, no. 9, pp. 1077–1083, 1996. View at Publisher · View at Google Scholar · View at Scopus
  11. R. M. Lyons, J. Keski-Oja, and H. L. Moses, “Proteolytic activation of latent transforming growth factor-β from fibroblast-conditioned medium,” Journal of Cell Biology, vol. 106, no. 5, pp. 1659–1665, 1988. View at Publisher · View at Google Scholar · View at Scopus
  12. E. J. Ehrhart, P. Segarini, M. L.-S. Tsang, A. G. Carroll, and M. H. Barcellos-Hoff, “Latent transforming growth factor β1 activation in situ: quantitative and functional evidence after low-dose γ-irradiation,” The FASEB Journal, vol. 11, no. 12, pp. 991–1002, 1997. View at Google Scholar · View at Scopus
  13. F. Verrecchia, M. Chu, and A. Mauviel, “Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach,” Journal of Biological Chemistry, vol. 276, no. 20, pp. 17058–17062, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. S. N. Flier, H. Tanjore, E. G. Kokkotou, H. Sugimoto, M. Zeisberg, and R. Kalluri, “Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis,” Journal of Biological Chemistry, vol. 285, no. 26, pp. 20202–20212, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. E. M. Zeisberg, O. Tarnavski, M. Zeisberg et al., “Endothelial-to-mesenchymal transition contributes to cardiac fibrosis,” Nature Medicine, vol. 13, no. 8, pp. 952–961, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Rieder and C. Fiocchi, “Intestinal fibrosis in IBD—a dynamic, multifactorial process,” Nature Reviews Gastroenterology and Hepatology, vol. 6, no. 4, pp. 228–235, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Barrientos, O. Stojadinovic, M. S. Golinko, H. Brem, and M. Tomic-Canic, “Growth factors and cytokines in wound healing,” Wound Repair and Regeneration, vol. 16, no. 5, pp. 585–601, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. J. G. Abreu, N. I. Ketpura, B. Reversade, and E. M. De Robertis, “Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-β,” Nature Cell Biology, vol. 4, no. 8, pp. 599–604, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. M. R. Duncan, K. S. Frazier, S. Abramson et al., “Connective tissue growth factor mediates transforming growth factor β-induced collagen synthesis: Downregulation by cAMP,” FASEB Journal, vol. 13, no. 13, pp. 1774–1786, 1999. View at Google Scholar · View at Scopus
  20. B. S. Weston, N. A. Wahab, and R. M. Mason, “CTGF mediates TGF-β-induced fibronectin matrix deposition by upregulating active α5β1 integrin in human mesangial cells,” Journal of the American Society of Nephrology, vol. 14, no. 3, pp. 601–610, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. E. H. Choi, N. Lee, H. J. Kim et al., “Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes,” Genes and Nutrition, vol. 2, no. 4, pp. 337–345, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. J. R. Teerlink, J. M. Pfeffer, and M. A. Pfeffer, “Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats,” Circulation Research, vol. 75, no. 1, pp. 105–113, 1994. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Nishikimi, K. Uchino, and E. D. Frohlich, “Effects of α1-adrenergic blockade on intrarenal hemodynamics in heart failure rats,” The American Journal of Physiology: Regulatory Integrative and Comparative Physiology, vol. 262, no. 2, part 2, pp. R198–R203, 1992. View at Google Scholar · View at Scopus
  24. A. L. Cochrane, M. M. Kett, C. S. Samuel et al., “Renal structural and functional repair in a mouse model of reversal of ureteral obstruction,” Journal of the American Society of Nephrology, vol. 16, no. 12, pp. 3623–3630, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. V. H. Urbieta-Caceres, R. Lavi, X.-Y. Zhu et al., “Early atherosclerosis aggravates the effect of renal artery stenosis on the swine kidney,” The American Journal of Physiology, vol. 299, no. 1, pp. F135–F140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. L. O. Lerman, R. S. Schwartz, J. P. Grande, P. F. Sheedy II, and J. C. Romero, “Noninvasive evaluation of a novel swine model of renal artery stenosis,” Journal of the American Society of Nephrology, vol. 10, no. 7, pp. 1455–1465, 1999. View at Google Scholar · View at Scopus
  27. I. Herrero-Fresneda, J. Torras, A. Vidal, N. Lloberas, J. M. Cruzado, and J. M. Grinyó, “Reduction of postischemic immune inflammatory response: an effective strategy for attenuating chronic allograft nephropathy,” Transplantation, vol. 79, no. 2, pp. 165–173, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Chaaya, C. Alfarano, C. Guilbeau-Frugier et al., “Pargyline reduces renal damage associated with ischaemia-reperfusion and cyclosporin,” Nephrology Dialysis Transplantation, vol. 26, no. 2, pp. 489–498, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Fleck, D. Appenroth, P. Jonas et al., “Suitability of 5/6 nephrectomy (5/6NX) for the induction of interstitial renal fibrosis in rats: influence of sex, strain, and surgical procedure,” Experimental and Toxicologic Pathology, vol. 57, no. 3, pp. 195–205, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. L. W. D. Weber, M. Boll, and A. Stampfl, “Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model,” Critical Reviews in Toxicology, vol. 33, no. 2, pp. 105–136, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. C. A. Claussen and E. C. Long, “Nucleic acid recognition by metal complexes of bleomycin,” Chemical Reviews, vol. 99, no. 9, pp. 2797–2816, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. B. B. Moore and C. M. Hogaboam, “Murine models of pulmonary fibrosis,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 294, no. 2, pp. L152–L160, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. B. J. R. Junor, J. D. Briggs, and M. A. Forwell, “Sclerosing peritonitis–the contribution of chlorhexidine in alcohol,” Peritoneal Dialysis Bulletin, vol. 5, no. 2, pp. 101–104, 1985. View at Google Scholar · View at Scopus
  34. T. Yamamoto, S. Takagawa, I. Katayama et al., “Animal model of sclerotic skin. I: Local injections of bleomycin induce sclerotic skin mimicking scleroderma,” Journal of Investigative Dermatology, vol. 112, no. 4, pp. 456–462, 1999. View at Publisher · View at Google Scholar · View at Scopus
  35. J. A. Horton, E. J. Chung, K. E. Hudak et al., “Inhibition of radiation-induced skin fibrosis with imatinib,” International Journal of Radiation Biology, vol. 89, no. 3, pp. 162–170, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Peters, A. Sindrilaru, B. Hinz et al., “Wound-healing defect of CD18-/- mice due to a decrease in TGF-β1 and myofibroblast differentiation,” The EMBO Journal, vol. 24, no. 19, pp. 3400–3410, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. R. J. Berry, G. Wiernik, T. J. S. Patterson, and J. W. Hopewell, “Excess late subcutaneous fibrosis after irradiation of pig skin, consequent upon the application of the NSD formula,” British Journal of Radiology, vol. 47, no. 557, pp. 277–281, 1974. View at Publisher · View at Google Scholar · View at Scopus
  38. N. Hazra and M. Gulliford, “Evaluating pancreatitis in primary care: a population-based cohort study,” The British Journal of General Practice, vol. 64, no. 622, pp. e295–e301, 2014. View at Google Scholar
  39. J. Merkord, L. Jonas, H. Weber, G. Kröning, H. Nizze, and G. Hennighausen, “Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions,” Pancreas, vol. 15, no. 4, pp. 392–401, 1997. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Linard, E. Busson, V. Holler et al., “Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs,” Stem Cells Translational Medicine, vol. 2, no. 11, pp. 916–927, 2013. View at Google Scholar
  41. L. Song, Y. J. Yang, Q. T. Dong et al., “Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase,” PLoS ONE, vol. 8, no. 5, Article ID e65702, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. S. M. Gorji, A. A. K. Malekshah, M. B. Hashemi-Soteh, A. Rafiei, K. Parivar, and N. Aghdami, “Effect of mesenchymal stem cells on doxorubicin-induced fibrosis,” Cell Journal, vol. 14, no. 2, pp. 142–151, 2012. View at Google Scholar · View at Scopus
  43. L. Li, Y. Zhang, Y. Li et al., “Mesenchymal stem cell transplantation attenuates cardiac fibrosis associated with isoproterenol-induced global heart failure,” Transplant International, vol. 21, no. 12, pp. 1181–1189, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. C. Mias, O. Lairez, E. Trouche et al., “Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction,” Stem Cells, vol. 27, no. 11, pp. 2734–2743, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Ishikane, H. Hosoda, K. Yamahara et al., “Allogeneic transplantation of fetal membrane-derived mesenchymal stem cell sheets increases neovascularization and improves cardiac function after myocardial infarction in rats,” Transplantation, vol. 96, no. 8, pp. 697–706, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. G. A. Nasir, S. Mohsin, M. Khan et al., “Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice,” Journal of Translational Medicine, vol. 11, no. 1, article 78, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Li, Y. Yan, B. Wang et al., “Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis,” Stem Cells and Development, vol. 22, no. 6, pp. 845–854, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. V. Rabani, M. Shahsavani, M. Gharavi, A. Piryaei, Z. Azhdari, and H. Baharvand, “Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression,” Cell Biology International, vol. 34, no. 6, pp. 601–605, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. B. Fang, M. Shi, L. Liao, S. Yang, Y. Liu, and R. C. Zhao, “Systemic infusion of FLK1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice,” Transplantation, vol. 78, no. 1, pp. 83–88, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. G. Ali, S. Mohsin, M. Khan et al., “Nitric oxide augments mesenchymal stem cell ability to repair liver fibrosis,” Journal of Translational Medicine, vol. 10, no. 1, article 75, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Pan, P. Wang, L. Xiang, and J. Shao, “Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation,” Journal of Biological Chemistry, vol. 286, no. 14, pp. 12340–12348, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. D. Zhang, M. Jiang, and D. Miao, “Transplanted human amniotic membrane-derived mesenchymal stem cells ameliorate carbon tetrachloride-induced liver cirrhosis in mouse,” PLoS ONE, vol. 6, no. 2, Article ID e16789, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. Y. Wang, F. Lian, J. Li et al., “Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats,” Journal of Translational Medicine, vol. 10, no. 1, article 133, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Oyagi, M. Hirose, M. Kojima et al., “Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats,” Journal of Hepatology, vol. 44, no. 4, pp. 742–748, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. M. T. Abdel Aziz, H. M. Atta, S. Mahfouz et al., “Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis,” Clinical Biochemistry, vol. 40, no. 12, pp. 893–899, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. Y. Chang, J. Liu, P. Lin et al., “Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis,” Life Sciences, vol. 85, no. 13-14, pp. 517–525, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Hardjo, M. Miyazaki, M. Sakaguchi et al., “Suppression of carbon tetrachloride-induced liver fibrosis by transplantation of a clonal mesenchymal stem cell line derived from rat bone marrow,” Cell Transplantation, vol. 18, no. 1, pp. 89–99, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Qiao, Y. Tong, H. Han et al., “A novel therapeutic regimen for hepatic fibrosis using the combination of mesenchymal stem cells and baicalin,” Pharmazie, vol. 66, no. 1, pp. 37–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. P. Tsai, T. Fu, Y. A. Chen et al., “The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis,” Liver Transplantation, vol. 15, no. 5, pp. 484–495, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. Z. M. Bai, X. D. Deng, J. D. Li et al., “Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis,” Chinese Medical Journal, vol. 126, no. 10, pp. 1890–1894, 2013. View at Google Scholar · View at Scopus
  61. B. Ebrahimi, A. Eirin, Z. Li et al., “Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis,” PLoS ONE, vol. 8, no. 7, Article ID e67474, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. H. J. Wu, W. H. Yiu, R. X. Li et al., “Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis,” PLoS One, vol. 9, no. 3, Article ID e90883, 2014. View at Google Scholar
  63. M. Franquesa, E. Herrero, J. Torras et al., “Mesenchymal stem cell therapy prevents interstitial fibrosis and tubular atrophy in a rat kidney allograft model,” Stem Cells and Development, vol. 21, no. 17, pp. 3125–3135, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Alfarano, C. Roubeix, R. Chaaya et al., “Intraparenchymal Injection of bone marrow mesenchymal stem cells reduces kidney fibrosis after ischemia-reperfusion in cyclosporine-immunosuppressed rats,” Cell Transplantation, vol. 21, no. 9, pp. 2009–2019, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Semedo, M. Correa-Costa, M. A. Cenedeze et al., “Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model,” Stem Cells, vol. 27, no. 12, pp. 3063–3073, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. H. Asanuma, B. A. Vanderbrink, M. T. Campbell et al., “Arterially delivered mesenchymal stem cells prevent obstruction-induced renal fibrosis,” Journal of Surgical Research, vol. 168, no. 1, pp. e51–e59, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Moodley, D. Atienza, U. Manuelpillai et al., “Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury,” American Journal of Pathology, vol. 175, no. 1, pp. 303–313, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. L. A. Ortiz, F. Gambelli, C. McBride et al., “Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 14, pp. 8407–8411, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. M. Choi, T. Ban, and T. Rhim, “Therapeutic use of stem cell transplantation for cell replacement or cytoprotective effect of microvesicle released from mesenchymal stem cell,” Molecules and Cells, vol. 37, no. 2, pp. 133–139, 2014. View at Google Scholar
  70. S. Lee, A. Jang, Y. Kim et al., “Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis,” Respiratory Research, vol. 11, article 16, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. F. Zhao, Y. F. Zhang, Y. G. Liu et al., “Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats,” Transplantation Proceedings, vol. 40, no. 5, pp. 1700–1705, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Gazdhar, N. Susuri, K. Hostettler et al., “HGF expressing stem cells in usual interstitial pneumonia originate from the bone marrow and are antifibrotic,” PLoS ONE, vol. 8, no. 6, Article ID e65453, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Ueno, A. Nakashima, S. Doi et al., “Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 signaling,” Kidney International, vol. 84, no. 2, pp. 297–307, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. C. H. Zhou, M. L. Li, A. L. Qin et al., “Reduction of fibrosis in dibutyltin dichloride-induced chronic pancreatitis using rat umbilical mesenchymal stem cells from Wharton's jelly,” Pancreas, vol. 42, no. 8, pp. 1291–1302, 2013. View at Google Scholar
  75. Y. Wu, S. Huang, J. Enhe et al., “Bone marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice,” International Wound Journal, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. J. A. Horton, K. E. Hudak, E. J. Chung et al., “Mesenchymal stem cells inhibit cutaneous radiation-induced fibrosis by suppressing chronic inflammation,” Stem Cells, vol. 31, no. 10, pp. 2231–2241, 2013. View at Google Scholar
  77. Y. Qi, D. Jiang, A. Sindrilaru et al., “TSG-6 Released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds,” Journal of Investigative Dermatology, vol. 134, no. 2, pp. 526–537, 2014. View at Publisher · View at Google Scholar
  78. P. Mok, C. Leong, and S. Cheong, “Cellular mechanisms of emerging applications of mesenchymal stem cells,” Malaysian Journal of Pathology, vol. 35, no. 1, pp. 17–32, 2013. View at Google Scholar · View at Scopus
  79. N. G. Singer and A. I. Caplan, “Mesenchymal stem cells: Mechanisms of inflammation,” Annual Review of Pathology: Mechanisms of Disease, vol. 6, pp. 457–478, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Corcione, F. Benvenuto, E. Ferretti et al., “Human mesenchymal stem cells modulate B-cell functions,” Blood, vol. 107, no. 1, pp. 367–372, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Keating, “How do mesenchymal stromal cells suppress T cells?” Cell Stem Cell, vol. 2, no. 2, pp. 106–108, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. F. Bifari, V. Lisi, E. Mimiola, A. Pasini, and M. Krampera, “Immune modulation by mesenchymal stem cells,” Transfusion Medicine and Hemotherapy, vol. 35, no. 3, pp. 194–204, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. P. A. Sotiropoulou, S. A. Perez, A. D. Gritzapis, C. N. Baxevanis, and M. Papamichail, “Interactions between human mesenchymal stem cells and natural killer cells,” Stem Cells, vol. 24, no. 1, pp. 74–85, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. Y. Taniyama, R. Morishita, M. Aoki et al., “Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy,” Hypertension, vol. 40, no. 1, pp. 47–53, 2002. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. T. Chen, C. K. Sun, Y. C. Lin et al., “Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction,” Journal of Translational Medicine, vol. 9, article 51, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. C. K. Sun, C. H. Yen, Y. C. Lin et al., “Autologous transplantation of adipose-derived mesenchymal stem cells markedly reduced acute ischemia-reperfusion lung injury in a rodent model,” Journal of Translational Medicine, vol. 9, no. 1, article 118, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. S. Francois, M. Mouiseddine, B. Allenet-Lepage et al., “Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation, and trophic effects,” BioMed Research International, vol. 2014, Article ID 151679, 14 pages, 2014. View at Publisher · View at Google Scholar
  88. K. Kemp, K. Hares, E. Mallam, K. J. Heesom, N. Scolding, and A. Wilkins, “Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival,” Journal of Neurochemistry, vol. 114, no. 6, pp. 1569–1580, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Kinnaird, E. Stabile, M. S. Burnett et al., “Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms,” Circulation Research, vol. 94, no. 5, pp. 678–685, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. S. C. Hung, R. R. Pochampally, S. C. Chen, S. C. Hsu, and D. J. Prockop, “Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis,” Stem Cells, vol. 25, no. 9, pp. 2363–2370, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. J. Niu, A. Azfer, O. Zhelyabovska, S. Fatma, and P. E. Kolattukudy, “Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP),” The Journal of Biological Chemistry, vol. 283, no. 21, pp. 14542–14551, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. T. Kinnaird, E. S. Burnett, M. Shou et al., “Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms,” Circulation, vol. 109, no. 12, pp. 1543–1549, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Rehman, D. Traktuev, J. Li et al., “Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells,” Circulation, vol. 109, no. 10, pp. 1292–1298, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Strup-Perrot, D. Mathé, C. Linard et al., “Global gene expression profiles reveal an increase in mRNA levels of collagens, MMPs, and TIMPs in late radiation enteritis,” American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 287, no. 4, pp. G875–G885, 2004. View at Publisher · View at Google Scholar · View at Scopus
  95. D. Reinhardt, H. H. Sigusch, J. Henße, S. C. Tyagi, R. Körfer, and H. R. Figulla, “Cardiac remodelling in end stage heart failure: Upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP,” Heart, vol. 88, no. 5, pp. 525–530, 2002. View at Publisher · View at Google Scholar · View at Scopus
  96. D. Vanhoutte, M. Schellings, Y. Pinto, and S. Heymans, “Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: a temporal and spatial window,” Cardiovascular Research, vol. 69, no. 3, pp. 604–613, 2006. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Cheng, A. S. Pollock, R. Mahimkar, J. L. Olson, and D. H. Lovett, “Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury,” The FASEB Journal, vol. 20, no. 11, pp. 1898–1900, 2006. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Yaguchi, Y. Fukuda, M. Ishizaki, and N. Yamanaka, “Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis,” Pathology International, vol. 48, no. 12, pp. 954–963, 1998. View at Publisher · View at Google Scholar · View at Scopus
  99. C. Mias, E. Trouche, M. H. Seguelas et al., “Ex vivo pretreatment with melatonin improves survival, proangiogenic/ mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney,” Stem Cells, vol. 26, no. 7, pp. 1749–1757, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. H. K. Yip, Y. C. Chang, C. G. Wallace et al., “Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury,” Journal of Pineal Research, vol. 54, no. 2, pp. 207–221, 2013. View at Publisher · View at Google Scholar · View at Scopus
  101. C. L. Visage, O. Gournay, N. Benguirat et al., “Mesenchymal stem cell delivery into rat infarcted myocardium using a porous polysaccharide-based scaffold: a quantitative comparison with endocardial injection,” Tissue Engineering A, vol. 18, no. 1-2, pp. 35–44, 2012. View at Publisher · View at Google Scholar · View at Scopus
  102. C. Ceccaldi, R. Bushkalova, C. Alfarano et al., “Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment,” Acta Biomaterialia, vol. 10, no. 2, pp. 901–911, 2014. View at Google Scholar
  103. M. M. Lalu, L. McIntyre, C. Pugliese et al., “Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials,” PLoS ONE, vol. 7, no. 10, Article ID e47559, 2012. View at Publisher · View at Google Scholar · View at Scopus
  104. K. C. Rustad and G. C. Gurtner, “Mesenchymal stem cells home to sites of injury and inflammation,” Advances in Wound Care, vol. 1, no. 4, pp. 147–152, 2012. View at Google Scholar
  105. M. Mohamadnejad, K. Alimoghaddam, M. Mohyeddin-Bonab et al., “Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis,” Archives of Iranian Medicine, vol. 10, no. 4, pp. 459–466, 2007. View at Google Scholar · View at Scopus
  106. P. Kharaziha, P. M. Hellström, B. Noorinayer et al., “Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial,” European Journal of Gastroenterology and Hepatology, vol. 21, no. 10, pp. 1199–1205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. Z. Zhang, H. Lin, M. Shi et al., “Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients,” Journal of Gastroenterology and Hepatology, vol. 27, supplement 2, pp. 112–120, 2012. View at Publisher · View at Google Scholar · View at Scopus
  108. P. S. Kamath, R. H. Wiesner, M. Malinchoc et al., “A model to predict survival in patients with end-stage liver disease,” Hepatology, vol. 33, no. 2, pp. 464–470, 2001. View at Publisher · View at Google Scholar · View at Scopus
  109. J. E. Ware Jr. and C. D. Sherbourne, “The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection,” Medical Care, vol. 30, no. 6, pp. 473–483, 1992. View at Publisher · View at Google Scholar · View at Scopus
  110. M. E. J. Reinders, J. W. de Fijter, H. Roelofs et al., “Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation:Results of a phase I study,” Stem Cells Translational Medicine, vol. 2, no. 2, pp. 107–111, 2013. View at Publisher · View at Google Scholar · View at Scopus
  111. J. M. Hare, J. H. Traverse, T. D. Henry et al., “A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction,” Journal of the American College of Cardiology, vol. 54, no. 24, pp. 2277–2286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. J. M. Hare, J. E. Fishman, G. Gerstenblith et al., “Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial,” JAMA, vol. 308, no. 22, pp. 2369–2379, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. S. Saito, G. Matsumiya, T. Sakaguchi et al., “Cardiac fibrosis and cellular hypertrophy decrease the degree of reverse remodeling and improvement in cardiac function during left ventricular assist,” Journal of Heart and Lung Transplantation, vol. 29, no. 6, pp. 672–679, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. J. J. Lataillade, C. Doucet, E. Bey et al., “New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy,” Regenerative Medicine, vol. 2, no. 5, pp. 785–794, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Rafii, M. M. Juarez, T. E. Albertson, and A. L. Chan, “A review of current and novel therapies for idiopathic pulmonary fibrosis,” Journal of Thoracic Disease, vol. 5, no. 1, pp. 48–73, 2013. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Salazar-Montes, L. Ruiz-Corro, A. López-Reyes, E. Castrejón-Gómez, and J. Armendáriz-Borunda, “Potent antioxidant role of Pirfenidone in experimental cirrhosis,” European Journal of Pharmacology, vol. 595, no. 1–3, pp. 69–77, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. S. N. Iyer, G. Gurujeyalakshmi, and S. N. Giri, “Effects of pirfenidone on transforming growth factor-β gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis,” Journal of Pharmacology and Experimental Therapeutics, vol. 291, no. 1, pp. 367–373, 1999. View at Google Scholar · View at Scopus
  118. S. Mirkovic, A. L. Seymour, A. Fenning et al., “Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats,” British Journal of Pharmacology, vol. 135, no. 4, pp. 961–968, 2002. View at Publisher · View at Google Scholar · View at Scopus
  119. K. Takakuta, A. Fujimori, T. Chikanishi et al., “Renoprotective properties of pirfenidone in subtotally nephrectomized rats,” European Journal of Pharmacology, vol. 629, no. 1–3, pp. 118–124, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. A. di Sario, E. Bendia, G. Macarri et al., “The anti-fibrotic effect of pirfenidone in rat liver fibrosis is mediated by downregulation of procollagen α1(I), TIMP-1 and MMP-2,” Digestive and Liver Disease, vol. 36, no. 11, pp. 744–751, 2004. View at Publisher · View at Google Scholar · View at Scopus
  121. N. L. Simone, B. P. Soule, L. Gerber et al., “Oral pirfenidone in patients with chronic fibrosis resulting from radiotherapy: a pilot study,” Radiation Oncology, vol. 2, no. 1, article 19, 2007. View at Publisher · View at Google Scholar · View at Scopus
  122. Pulmonary-Allergy Drugs Advisory Committee Complete Response on Pirfenidone, Food and Drug Administration Center for Drug Evaluation and Research, March 2010, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM206399.pdf.
  123. C. Jiang, H. Huang, J. Liu, Y. Wang, Z. Lu, and Z. Xu, “Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials,” PLoS ONE, vol. 7, no. 10, Article ID e47024, 2012. View at Publisher · View at Google Scholar · View at Scopus
  124. J. Rosenbloom, F. A. Mendoza, and S. A. Jimenez, “Strategies for anti-fibrotic therapies,” Biochimica et Biophysica Acta: Molecular Basis of Disease, vol. 1832, no. 7, pp. 1088–1103, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. M. A. Ngo, A. Muller, Y. Li et al., “Human mesenchymal stem cells express a myofibroblastic phenotype in vitro: comparison to human cardiac myofibroblasts,” Molecular and Cellular Biochemistry, vol. 392, no. 1-2, pp. 187–204, 2014. View at Publisher · View at Google Scholar
  126. L. Yang, N. Chang, X. Liu et al., “Bone marrow-derived mesenchymal stem cells differentiate to hepatic myofibroblasts by transforming growth factor-β1 via sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis,” The American Journal of Pathology, vol. 181, no. 1, pp. 85–97, 2012. View at Publisher · View at Google Scholar · View at Scopus
  127. S. Chakraborty, P. Chopra, A. Hak, S. G. Dastidar, and A. Ray, “Hepatocyte growth factor is an attractive target for the treatment of pulmonary fibrosis,” Expert Opinion on Investigational Drugs, vol. 22, no. 4, pp. 499–515, 2013. View at Publisher · View at Google Scholar · View at Scopus