Mesenchymal stem/stromal cells in liver fibrosis: Recent findings, old/new caveats and future perspectives

Stem Cell Reviews and Reports

Volumn 11, Issue 4, 2015, Pages 586-597

  Fiore, Esteban J ^a   Mazzolini, Guillermo ^a,b   Aquino, Jorge B ^a,b  

^a UNIVERSIDAD AUSTRAL   (Argentina)

^b Facultad de Ciencias Naturales e Instituto M Lillo   (Argentina)

Author keywords

Biodistribution; Biosafety; Cell source; Cirrhosis; Hepatocyte like cells; IGF I; Mechanisms; Mesenchymal stemcells; Neural crest

Indexed keywords

ANIMAL; BIOLOGICAL MODEL; CELL DIFFERENTIATION; CELL PROLIFERATION; CYTOLOGY; HUMAN; LIVER CIRRHOSIS; LIVER REGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMA CELL; PATHOPHYSIOLOGY; PHYSIOLOGY; PROCEDURES; REGENERATIVE MEDICINE; TRENDS;

ANIMALS; CELL DIFFERENTIATION; CELL PROLIFERATION; HUMANS; LIVER CIRRHOSIS; LIVER REGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; MODELS, BIOLOGICAL; REGENERATIVE MEDICINE;

EID: 84943365822     PISSN: 15508943     EISSN: 15586804     Source Type: Journal    
DOI: 10.1007/s12015-015-9585-9     Document Type: Article

References (137)

1. Bataller, R., & Brenner, D. A. (2005). Liver fibrosis. Journal of Clinical Investigation, 115, 209-218.
2. Iwaisako, K., Jiang, C., Zhang, M., et al. (2014). Origin of myofibroblasts in the fibrotic liver in mice. Proceedings of the National Academy of Sciences of the United States of America, 111, E3297-E3305.
3. Brenner, D. A. (2013). Reversibility of liver fibrosis. Gastroenterology and Hepatology, 9, 737-739.
4. Abdel Aziz, M. T., Atta, H. M., Mahfouz, S., et al. (2007). Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clinical Biochemistry, 40, 893-899.
5. Fang, B., Shi, M., Liao, L., Yang, S., Liu, Y., & Zhao, R. C. (2004). Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation, 78, 83-88.
6. Aquino, J. B., Bolontrade, M. F., Garcia, M. G., Podhajcer, O. L., & Mazzolini, G. (2010). Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma. Gene Therapy, 17, 692-708.
7. Berardis, S., Dwisthi Sattwika, P., Najimi, M., & Sokal, E. M. (2015). Use of mesenchymal stemcells to treat liver fibrosis: current situation and future prospects. World Journal of Gastroenterology, 21, 742-758.
8. Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143-147.
9. Li, M., & Ikehara, S. (2013). Bone-marrow-derived mesenchymal stem cells for organ repair. Stem Cells International, 2013, 132642.
10. Bayo, J., Marrodan, M., Aquino, J.B., Silva, M., Garcia, M.G., Mazzolini, G. (2013). The therapeutic potential of bone marrowderived mesenchymal stromal cells on hepatocellular carcinoma. Liver International.
11. Bakondi, B., Shimada, I. S., Perry, A., et al. (2009). CD133 identifies a human bone marrow stem/progenitor cell sub-population with a repertoire of secreted factors that protect against stroke. Molecular Therapy, 17, 1938-1947.
12. John, N., Cinelli, P., Wegner, M., & Sommer, L. (2011). Transforming growth factor beta-mediated Sox10 suppression controls mesenchymal progenitor generation in neural crest stem cells. Stem Cells, 29, 689-699.
13. Wislet-Gendebien, S., Laudet, E., Neirinckx, V., et al. (2012). Mesenchymal stemcells and neural crest stem cells from adult bonemarrow: characterization of their surprising similarities and differences. Cellular and Molecular Life Sciences, 69, 2593-2608.
14. Morikawa, S., Mabuchi, Y., Niibe, K., et al. (2009). Development of mesenchymal stem cells partially originate from the neural crest. Biochemical and Biophysical Research Communications, 379, 1114-1119.
15. Takashima, Y., Era, T., Nakao, K., et al. (2007). Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell, 129, 1377-1388.
16. Mendez-Ferrer, S., Michurina, T. V., Ferraro, F., et al. (2010). Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 466, 829-834.
17. Adameyko, I., Lallemend, F., Aquino, J. B., et al. (2009). Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell, 139, 366-379.
18. Isern, J., Garcia-Garcia, A., Martin, A. M., et al. (2014). The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function. Elife, 3, e03696.
19. Kaukua, N., Shahidi, M. K., Konstantinidou, C., et al. (2014). Glial origin of mesenchymal stem cells in a tooth model system. Nature, 513, 551-554.
20. Bianco, P., Cao, X., Frenette, P. S., et al. (2013). The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nature Medicine, 19, 35-42.
21. Corselli, M., Chin, C. J., Parekh, C., et al. (2013). Perivascular support of human hematopoietic stem/progenitor cells. Blood, 121, 2891-2901.
22. Sacchetti, B., Funari, A., Michienzi, S., et al. (2007). Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell, 131, 324-336.
23. Bakondi, B., & Spees, J. L. (2010). Human CD133-derived bone marrow stromal cells establish ectopic hematopoietic microenvironments in immunodeficient mice. Biochemical and Biophysical Research Communications, 400, 212-218.
24. Rasini, V., Dominici, M., Kluba, T., et al. (2013). Mesenchymal stromal/stem cells markers in the human bone marrow. Cytotherapy, 15, 292-306.
25. Kuroda, Y., Kitada, M., Wakao, S., & Dezawa, M. (2011). Bone marrow mesenchymal cells: how do they contribute to tissue repair and are they really stem cells? Archivum Immunologiae et Therapiae Experimentalis (Warsz), 59, 369-378.
26. Le Lievre, C. S., & Le Douarin, N. M. (1975).Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. Journal of Embryology and Experimental Morphology, 34, 125-154.
27. Binato, R., de Souza, F. T., Lazzarotto-Silva, C., et al. (2013). Stability of human mesenchymal stem cells during in vitro culture: considerations for cell therapy. Cell Proliferation, 46, 10-22.
28. Foudah, D., Redondo, J., Caldara, C., Carini, F., Tredici, G., & Miloso, M. (2012). Expression of neural markers by undifferentiated rat mesenchymal stem cells. Journal of Biomedicine and Biotechnology, 2012, 820821.
29. Puglisi, M. A., Tesori, V., Lattanzi, W., et al. (2011). Therapeutic implications of mesenchymal stem cells in liver injury. Journal of Biomedicine and Biotechnology, 2011, 860578.
30. Ayatollahi, M., Soleimani, M., Tabei, S. Z., & Kabir, S. M. (2011). Hepatogenic differentiation of mesenchymal stem cells induced by insulin like growth factor-I. World Journal of Stem Cells, 3, 113-121.
31. He, H., Liu, X., Peng, L., et al. (2013). Promotion of hepatic differentiation of bone marrow mesenchymal stem cells on decellularized cell-deposited extracellular matrix. BioMed Research International, 2013, 406871.
32. Piryaei, A., Valojerdi, M. R., Shahsavani, M., & Baharvand, H. (2011). Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells on nanofibers and their transplantation into a carbon tetrachloride-induced liver fibrosis model. Stem Cell Reviews, 7, 103-118.
33. Pournasr, B., Mohamadnejad, M., Bagheri, M., et al. (2011). In vitro differentiation of human bone marrow mesenchymal stem cells into hepatocyte-like cells. Archives of Iranian Medicine, 14, 244-249.
34. Aurich, H., Sgodda, M., Kaltwasser, P., et al. (2009). Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut, 58, 570-581.
35. Banas, A., Teratani, T., Yamamoto, Y., et al. (2007). Adipose tissuederived mesenchymal stem cells as a source of human hepatocytes. Hepatology, 46, 219-228.
36. Sun, J., Yuan, Y., Qin, H., et al. (2013). Serum from hepatectomized rats induces the differentiation of adipose tissue mesenchymal stem cells into hepatocyte-like cells and upregulates the expression of hepatocyte growth factor and interleukin-6 in vitro. International Journal of Molecular Medicine, 31, 667-675.
37. Cui, L., Zhou, X., Li, J., et al. (2012). Dynamic microRNA profiles of hepatic differentiated human umbilical cord lining-derived mesenchymal stem cells. PLoS One, 7, e44737.
38. Liang, X. J., Chen, X. J., Yang, D. H., Huang, S. M., Sun, G. D., & Chen, Y. P. (2012). Differentiation of human umbilical cord mesenchymal stem cells into hepatocyte-like cells by hTERT gene transfection in vitro. Cell Biology International, 36, 215-221.
39. Prasajak, P., & Leeanansaksiri, W. (2013). Developing a New Twostep protocol to generate functional hepatocytes from Wharton’s jelly-derived mesenchymal stem cells under hypoxic condition. Stem Cells International, 2013, 762196.
40. Bornstein, R., Macias, M. I., de la Torre, P., Grande, J., & Flores, A. I. (2012). Human decidua-derived mesenchymal stromal cells differentiate into hepatic-like cells and form functional threedimensional structures. Cytotherapy, 14, 1182-1192.
41. Volarevic, V., Nurkovic, J., Arsenijevic, N., & Stojkovic, M. (2014). Concise review: therapeutic potential of mesenchymal stemcells for the treatment of acute liver failure and cirrhosis. Stem Cells, 32, 2818-2823.
42. Meier, R. P., Muller, Y. D., Morel, P., Gonelle-Gispert, C., & Buhler, L. H. (2013). Transplantation of mesenchymal stem cells for the treatment of liver diseases, is there enough evidence? Stem Cell Research, 11, 1348-1364.
43. Kuroda, Y., Kitada, M., Wakao, S., et al. (2010). Uniquemultipotent cells in adult human mesenchymal cell populations. Proceedings of the National Academy of Sciences of the United States of America, 107, 8639-8643.
44. Ogura, F., Wakao, S., Kuroda, Y., et al. (2014). Human adipose tissue possesses a unique population of pluripotent stem cells with nontumorigenic and low telomerase activities: potential implications in regenerative medicine. Stem Cells and Development, 23, 717-728.
45. Bugianesi, E., Leone, N., Vanni, E., et al. (2002). Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology, 123, 134-140.
46. Barreyro, F.J., Holod, S., Finocchietto, P.V., et al. (2014). The pancaspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver International.
47. Kirchner, S., Kieu, T., Chow, C., Casey, S., & Blumberg, B. (2010). Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Molecular Endocrinology, 24, 526-539.
48. Yanik, S. C., Baker, A. H., Mann, K. K., & Schlezinger, J. J. (2011). Organotins are potent activators of PPARgamma and adipocyte differentiation in bonemarrowmultipotentmesenchymal stromal cells. Toxicological Sciences, 122, 476-488.
49. Thayer, K. A., Heindel, J. J., Bucher, J. R., & Gallo, M. A. (2012). Role of environmental chemicals in diabetes and obesity: a NationalToxicology Program workshop review. Environmental Health Perspectives, 120, 779-789.
50. Chamorro-Garcia, R., Sahu, M., Abbey, R. J., Laude, J., Pham, N., & Blumberg, B. (2013). Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice. Environmental Health Perspectives, 121, 359-366.
51. Cui, L., Shi, Y., Han, Y., & Fan, D. (2014). Immunological basis of stem cell therapy in liver diseases. Expert Review of Clinical Immunology, 10, 1185-1196.
52. Du Rocher, B., Mencalha, A. L., Gomes, B. E., & Abdelhay, E. (2012). Mesenchymal stromal cells impair the differentiation of CD14(++) CD16(−) CD64(+) classical monocytes into CD14(++) CD16(+) CD64(++) activate monocytes. Cytotherapy, 14, 12-25.
53. Zhang, Y., Cai, W., Huang, Q., et al. (2014). Mesenchymal stem cells alleviate bacteria-induced liver injury in mice by inducing regulatory dendritic cells. Hepatology, 59, 671-682.
54. Oh, J.Y., Ko, J.H., Lee, H.J., et al. (2013). Mesenchymal stem/stromal cells inhibit the NLRP3 inflammasome by decreasing mitochondrial reactive oxygen species. Stem Cells.
55. Gomez-Aristizabal, A., Ng, C., Ng, J., & Davies, J. E. (2012). Effects of two mesenchymal cell populations on hepatocytes and lymphocytes. Liver Transplantation, 18, 1384-1394.
56. Han, Z., Jing, Y., Zhang, S., Liu, Y., Shi, Y., & Wei, L. (2012). The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth. Cell & Bioscience, 2, 8.
57. Murphy, M. B., Moncivais, K., & Caplan, A. I. (2013). Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Experimental and Molecular Medicine, 45, e54.
58. Prockop, D. J., & Oh, J. Y. (2012).Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Molecular Therapy, 20, 14-20.
59. Chiesa, S., Morbelli, S., Morando, S., et al. (2011). Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 108, 17384-17389.
60. Sanchez-Abarca, L. I., Alvarez-Laderas, I., Diez Campelo, M., et al. (2013). Uptake and delivery of antigens by mesenchymal stromal cells. Cytotherapy, 15, 673-678.
61. 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.
62. Krampera, M., Galipeau, J., Shi, Y., Tarte, K., & Sensebe, L. (2013). Immunological characterization of multipotent mesenchymal stromal cells-The International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy, 15, 1054-1061.
63. Acquistapace, A., Bru, T., Lesault, P. F., et al. (2011). Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondria transfer. Stem Cells, 29, 812-824.
64. Johansson, C. B., Youssef, S., Koleckar, K., et al. (2008). Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation. Nature Cell Biology, 10, 575-583.
65. Shao, C. H., Chen, S. L., Dong, T. F., et al. (2014). Transplantation of bone marrow-derived mesenchymal stem cells after regional hepatic irradiation ameliorates thioacetamide-induced liver fibrosis in rats. Journal of Surgical Research, 186, 408-416.
66. Kim, S. J., Moon, G. J., Cho, Y. H., et al. (2012). Circulating mesenchymal stem cells microparticles in patients with cerebrovascular disease. PLoS One, 7, e37036.
67. Ma, J., Cai, W., Zhang, Y., et al. (2013). Innate immune cell-derived microparticles facilitate hepatocarcinoma metastasis by transferring integrin alpha(M)beta(2) to tumor cells. Journal of Immunology, 191, 3453-3461.
68. Masyuk, A. I., Masyuk, T. V., & Larusso, N. F. (2013). Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases. Journal of Hepatology, 59, 621-625.
69. Bruno, S., Grange, C., Deregibus, M. C., et al. (2009). Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. Journal of the American Society of Nephrology, 20, 1053-1067.
70. Herrera, M. B., Fonsato, V., Gatti, S., et al. (2010). Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. Journal of Cellular and Molecular Medicine, 14, 1605-1618.
71. Lin, C. S., Xin, Z. C., Dai, J., & Lue, T. F. (2013). Commonly used mesenchymal stemcellmarkers and tracking labels: Limitations and challenges. Histology and Histopathology, 28, 1109-1116.
72. Reagan, M. R., & Kaplan, D. L. (2011). Concise review: mesenchymal stem cell tumor-homing: detection methods in disease model systems. Stem Cells, 29, 920-927.
73. Coronel, M. F., Musolino, P. L., & Villar, M. J. (2006). Selective migration and engraftment of bonemarrow mesenchymal stem cells in rat lumbar dorsal root ganglia after sciatic nerve constriction. Neuroscience Letters, 405, 5-9.
74. Salguero Palacios, R., Roderfeld, M., Hemmann, S., et al. (2008). Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. Laboratory Investigation, 88, 1192-1203.
75. Ren, H., Zhao, Q., Cheng, T., et al. (2010). No contribution of umbilical cord mesenchymal stromal cells to capillarization and venularization of hepatic sinusoids accompanied by hepatic differentiation in carbon tetrachloride-induced mouse liver fibrosis. Cytotherapy, 12, 371-383.
76. Fiore, E.J., Bayo, J., Garcia, M.G., et al. (2014). Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice. Stem Cells and Development.
77. Hong, H. S., Lee, J., Lee, E., et al. (2009). A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells. Nature Medicine, 15, 425-435.
78. Novo, E., Busletta, C., Bonzo, L. V., et al. (2011). Intracellular reactive oxygen species are required for directional migration of resident and bone marrow-derived hepatic pro-fibrogenic cells. Journal of Hepatology, 54, 964-974.
79. Marquez-Curtis, L. A., & Janowska-Wieczorek, A. (2013). Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis. BioMed Research International, 2013, 561098.
80. Xie, J., Wang, W., Si, J. W., et al. (2013). Notch signaling regulates CXCR4 expression and the migration of mesenchymal stem cells. Cellular Immunology, 281, 68-75.
81. Lu, M. H., Li, C. Z., Hu, C. J., et al. (2012). microRNA-27b suppresses mouse MSC migration to the liver by targeting SDF- 1alphain vitro. Biochemical and Biophysical Research Communications, 421, 389-395.
82. Marquez-Curtis, L. A., Gul-Uludag, H., Xu, P., Chen, J., & Janowska-Wieczorek, A. (2013). CXCR4 transfection of cord blood mesenchymal stromal cells with the use of cationic liposome enhances their migration toward stromal cell-derived factor-1. Cytotherapy, 15, 840-849.
83. Eggenhofer, E., Benseler, V., Kroemer, A., et al. (2012). Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Frontiers in Immunology, 3, 297.
84. Li, Q., Zhou, X., Shi, Y., et al. (2013). In vivo tracking and comparison of the therapeutic effects ofMSCs and HSCs for liver injury. PLoS One, 8, e62363.
85. Kuo, T.K., Hung, S.P., Chuang, C.H., et al. (2008). Stem cell therapy for liver disease: parameters governing the success of usingbone marrow mesenchymal stem cells. Gastroenterology, 134, 2111-21, 21 e1-3.
86. Hamedi-Asl, P., Halabian, R., Bahmani, P., et al. (2012). Adenovirus-mediated expression of the HO-1 protein within MSCs decreased cytotoxicity and inhibited apoptosis induced by oxidative stresses. Cell Stress & Chaperones, 17, 181-190.
87. Mohammadzadeh, M., Halabian, R., Gharehbaghian, A., et al. (2012). Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity. Cell Stress & Chaperones, 17, 553-565.
88. Taghi, G. M., Ghasem Kashani Maryam, H., Taghi, L., Leili, H., & Leyla, M. (2012). Characterization of in vitro cultured bone marrow and adipose tissue-derived mesenchymal stem cells and their ability to express neurotrophic factors. Cell Biology International, 36, 1239-1249.
89. Helledie, T., Dombrowski, C., Rai, B., et al. (2012). Heparan sulfate enhances the self-renewal and therapeutic potential ofmesenchymal stem cells from human adult bone marrow. Stem Cells and Development, 21, 1897-1910.
90. Estrada, J. C., Albo, C., Benguria, A., et al. (2012). Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death and Differentiation, 19, 743-755.
91. Masoud, M. S., Anwar, S. S., Afzal, M. Z., Mehmood, A., Khan, S. N., & Riazuddin, S. (2012). Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment. Journal of Translational Medicine, 10, 243.
92. Ahmadbeigi, N., Soleimani, M., Babaeijandaghi, F., et al. (2012). The aggregate nature of humanmesenchymal stromal cells in native bone marrow. Cytotherapy, 14, 917-924.
93. Seki, A., Sakai, Y., Komura, T., et al. (2013). Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitisinduced cirrhosis model. Hepatology, 58, 1133-1142.
94. Zhang, Z., Lin, H., Shi, M., et al. (2012). Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. Journal of Gastroenterology and Hepatology, 27(Suppl 2), 112-120.
95. Forbes, S. J., & Newsome, P. N. (2012). New horizons for stem cell therapy in liver disease. Journal of Hepatology, 56, 496-499.
96. Li, T., Yan, Y., Wang, B., et al. (2013). Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells and Development, 22, 845-854.
97. Usunier, B., Benderitter, M., Tamarat, R., & Chapel, A. (2014). Management of fibrosis: the mesenchymal stromal cells breakthrough. Stem Cells International, 2014, 340257.
98. Li, T., Zhu, J., Ma, K., et al. (2013). Autologous bone marrowderived mesenchymal stem cell transplantation promotes liver regeneration after portal vein embolization in cirrhotic rats. Journal of Surgical Research, 184, 1161-1173.
99. Parekkadan, B., van Poll, D., Megeed, Z., et al. (2007). Immunomodulation of activated hepatic stellate cells bymesenchymal stem cells. Biochemical and Biophysical Research Communications, 363, 247-252.
100. Zhang, D., Jiang, M., & Miao, D. (2011). Transplanted human amniotic membrane-derived mesenchymal stem cells ameliorate carbon tetrachloride-induced liver cirrhosis in mouse. PLoS One, 6, e16789.
101. Cho, K. A., Woo, S.Y., Seoh, J.Y., Han, H. S., & Ryu, K.H. (2012). Mesenchymal stem cells restore CCl4-induced liver injury by an antioxidative process. Cell Biology International, 36, 1267-1274.
102. Nasir, G. A., Mohsin, S., Khan, M., et al. (2013). Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice. Journal of Translational Medicine, 11, 78.
103. Jung, J., Choi, J. H., Lee, Y., et al. (2013). Human placenta-derived mesenchymal stem cells promote hepatic regeneration in CCl4 - injured rat liver model via increased autophagic mechanism. Stem Cells, 31, 1584-1596.
104. Chagoya de Sanchez, V., Martinez-Perez, L., Hernandez-Munoz, R., & Velasco-Loyden, G. (2012). Recovery of the cell cycle inhibition in CCl(4)-induced cirrhosis by the adenosine derivative IFC- 305. International Journal of Hepatology, 2012, 212530.
105. Wang, H., Zhao, T., Xu, F., et al. (2014). How important is differentiation in the therapeutic effect of mesenchymal stromal cells in liver disease? Cytotherapy, 16, 309-318.
106. Madsen, D. H., Leonard, D., Masedunskas, A., et al. (2013). M2- likemacrophages are responsible for collagen degradation through a mannose receptor-mediated pathway. Journal of Cell Biology, 202, 951-966.
107. Bernardo, M. E., & Fibbe, W. E. (2013). Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell, 13, 392-402.
108. Li, Y., Wen, X., Spataro, B. C., Hu, K., Dai, C., & Liu, Y. (2006). Hepatocyte growth factor is a downstream effector that mediates the antifibrotic action of peroxisome proliferator-activated receptorgamma agonists. Journal of the American Society of Nephrology, 17, 54-65.
109. Wang, P. P., Xie, D. Y., Liang, X. J., et al. (2012). HGF and direct mesenchymal stem cells contact synergize to inhibit hepatic stellate cells activation through TLR4/NF-kB pathway. PLoS One, 7, e43408.
110. Di Nicola, M., Carlo-Stella, C., Magni, M., et al. (2002). Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 99, 3838-3843.
111. Yen, B. L., Yen, M. L., Hsu, P. J., et al. (2013). Multipotent human mesenchymal stromal cells mediate expansion of myeloid-derived suppressor cells via hepatocyte growth factor/c-Met and STAT3. Stem Cell Reports, 1, 139-151.
112. Atorrasagasti, C., Peixoto, E., Aquino, J. B., et al. (2013). Lack of the matricellular protein SPARC (secreted protein, acidic and rich in cysteine) attenuates liver fibrogenesis in mice. PLoS One, 8, e54962.
113. Bonefeld, K., & Moller, S. (2011). Insulin-like growth factor-I and the liver. Liver International, 31, 911-919.
114. Lee, M. W., Kim, D. S., Yoo, K. H., et al. (2013). Human bone marrow-derived mesenchymal stem cell gene expression patterns vary with culture conditions. Blood Research, 48, 107-114.
115. Kim, M. D., Kim, S. S., Cha, H. Y., et al. (2014). Therapeutic effect of hepatocyte growth factor-secreting mesenchymal stem cells in a rat model of liver fibrosis. Experimental and Molecular Medicine, 46, e110.
116. Tutau, F., Rodriguez-Ortigosa, C., Puche, J. E., et al. (2009). Enhanced actions of insulin-like growth factor-I and interferonalpha co-administration in experimental cirrhosis. Liver International, 29, 37-46.
117. Ali, G., Mohsin, S., Khan, M., et al. (2012). Nitric oxide augments mesenchymal stem cell ability to repair liver fibrosis. Journal of Translational Medicine, 10, 75.
118. Jang, Y. O., Kim, Y. J., Baik, S. K., et al. (2014). Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver International, 34, 33-41.
119. Lanzoni, G., Oikawa, T., Wang, Y., et al. (2013). Concise review: clinical programs of stem cell therapies for liver and pancreas. Stem Cells, 31, 2047-2060.
120. Ren, G., Chen, X., Dong, F., et al. (2012). Concise review: mesenchymal stem cells and translationalmedicine: emerging issues. Stem Cells Translational Medicine, 1, 51-58.
121. Shi, M., Zhang, Z., Xu, R., et al. (2012). Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on- 596 Stem Cell Rev and Rep (2015) 11:586-597 chronic liver failure patients. Stem Cells Translational Medicine, 1, 725-731.
122. Wang, L., Li, J., Liu, H., et al. (2013). Pilot study of umbilical cordderived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis. Journal of Gastroenterology and Hepatology, 28(Suppl 1), 85-92.
123. Sensebe, L., Gadelorge, M., & Fleury-Cappellesso, S. (2013). Production of mesenchymal stromal/stem cells according to good manufacturing practices: a review. Stem Cell Research & Therapy, 4, 66.
124. Barkholt, L., Flory, E., Jekerle, V., et al. (2013). Risk of tumorigenicity in mesenchymal stromal cell-based therapies-bridging scientific observations and regulatory viewpoints. Cytotherapy, 15, 753-759.
125. Pan, Q., Fouraschen, S. M., de Ruiter, P. E., et al. (2014). Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cells. Experimental Biology and Medicine (Maywood, N.J.), 239, 105-115.
126. Prockop, D. J., Brenner, M., Fibbe, W. E., et al. (2010). Defining the risks of mesenchymal stromal cell therapy. Cytotherapy, 12, 576-578.
127. Tarte, K., Gaillard, J., Lataillade, J. J., et al. (2010). Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood, 115, 1549-1553.
128. Prockop, D. J., & Keating, A. (2012). Relearning the lessons of genomic stability of human cells during expansion in culture: implications for clinical research. Stem Cells, 30, 1051-1052.
129. Estrada, J. C., Torres, Y., Benguria, A., et al. (2013). Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy. Cell Death & Disease, 4, e691.
130. Hanley, P. J., Mei, Z., da Graca, C.-H. M., et al. (2013). Manufacturingmesenchymal stromal cells for phase I clinical trials. Cytotherapy, 15, 416-422.
131. Chase, L. G., Yang, S., Zachar, V., et al. (2012). Development and characterization of a clinically compliant xeno-free culture medium in good manufacturing practice for human multipotent mesenchymal stem cells. Stem Cells Translational Medicine, 1, 750-758.
132. Chieregato, K., Castegnaro, S., Madeo, D., Astori, G., Pegoraro, M., & Rodeghiero, F. (2011). Epidermal growth factor, basic fibroblast growth factor and platelet-derived growth factor-bb can substitute for fetal bovine serum and compete with human platelet-rich plasma in the ex vivo expansion ofmesenchymal stromal cells derived from adipose tissue. Cytotherapy, 13, 933-943.
133. de Lima, P. K., de Santis, G. C., Orellana, M. D., Palma, P. V., Brassesco, M. S., & Covas, D. T. (2012). Cryopreservation of umbilical cordmesenchymal cells in xenofree conditions. Cytotherapy, 14, 694-700.
134. Julavijitphong, S., Wichitwiengrat, S., Tirawanchai, N., Ruangvutilert, P., Vantanasiri, C., & Phermthai, T. (2014). A xeno-free culture method that enhancesWharton’s jelly mesenchymal stromal cell culture efficiency over traditional animal serumsupplemented cultures. Cytotherapy, 16, 683-691.
135. Presson, A. P., Kim, N., Xiaofei, Y., Chen, I. S., & Kim, S. (2011). Methodology and software to detect viral integration site hot-spots. BMC Bioinformatics, 12, 367.
136. DeMatteo, R. P., Raper, S. E., Ahn, M., et al. (1995). Gene transfer to the thymus. A means of abrogating the immune response to recombinant adenovirus. Annals of Surgery, 222, 229-239. discussion 39-42.
137. Treacy, O., Ryan, A. E., Heinzl, T., et al. (2012). Adenoviral transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation. PLoS One, 7, e42662.