In Vitro Hepatocyte-Like Cells Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells
DOI:
https://doi.org/10.22100/jkh.v7i2.79Keywords:
Umbilical cord blood, Mesenchymal stem cells, Differentiation, Hepatocyte.Abstract
Introduction: Using stem cells for in vitro tissue regeneration is one of the most interesting fields of research. Liver regeneration is not an exceptional area. The main objective of this study was the production of hepatocyte- like cells from the umbilical cord blood mesenchymal stem cells (MSCs).
Methods: Cells were isolated from UCB, upon a written informed consent obtained from donor mothers. The stem cells immunophenotype was analyzed using flow cytometry and multi-lineage differentiation potential was evaluated by means of in vitro differentiation assays. Finally, the expression of hepatocyte-specific markers was verified using reverse transcription-polymerase chain reaction (RT-PCR).
Results: The isolated UCB-MSCs had mesodermal differentiation capacity. If UCB-MSCs are cultured in appropriate conditions, they are able to induce hepatic-associated genes, such as albumin (Alb),α-fetoprotein (AFP), cytokeratins 18, 19 (CK18, CK19) and α-1 antitrypsin (AA). Moreover, UCB- MSCs produced albumin and α-fetoprotein upon in vitro induction of hepatocyte differentiation.
Conclusion: Mesenchymal stem cells from human umbilical cord blood are capable of tissue-specific commitment along hepatogenic lineage, proposing these cells as suitable tool for cell-based applications aimed at liver regeneration.
References
References
Kazemnejad S, Allameh A, Soleimani M, Gharehbaghian A, Mohammadi Y, Amirizadeh N, et al. Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel three-dimensional biocompatible nanofibrous scaffold. J Gastroenterol Hepatol 2009;24:278-87.
Kazemnejad S, Allameh A, Soleimani M, Gharehbaghian A, Mohammadi Y, Amirizadeh N, et al. Development of a novel three-dimensional biocompatible nanofibrous scaffold for the expansion and hepatogenic differentiation of human bone marrow mesenchymal stem cells. Iran J Biotech 2007;5:201-11.[Persian].
Abdel Aziz MT, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Ahmed HH, et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem 2007;40:893-9.
References
Kazemnejad S, Allameh A, Soleimani M, Gharehbaghian A, Mohammadi Y, Amirizadeh N, et al. Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel three-dimensional biocompatible nanofibrous scaffold. J Gastroenterol Hepatol 2009;24:278-87.
Kazemnejad S, Allameh A, Soleimani M, Gharehbaghian A, Mohammadi Y, Amirizadeh N, et al. Development of a novel three-dimensional biocompatible nanofibrous scaffold for the expansion and hepatogenic differentiation of human bone marrow mesenchymal stem cells. Iran J Biotech 2007;5:201-11.[Persian].
Abdel Aziz MT, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Ahmed HH, et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem 2007;40:893-9.
Murphy JM FD, Hunziker EB. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004;36:568-84.
Kim YJ. Culture of umbilical cord- and cord blood-derived stem cells. Culture Of Human Stem Cells: John Wiley & Sons, Inc; 2007. p.156-86.
Kazemnejad S, Allameh A, Gharehbaghian A, Soleimani M, Amirizadeh N, Jazayeri M. Efficient replacing of fetal bovine serum with human platelet releasate during propagation and differentiation of human bone marrow-derived mesenchymal stem cells to functional hepatocytes-like cells. Vox Sang 2008;95:149-58.
Haynesworth SE, Baber MA, Caplan AI. Cell surface antigens on human bone marrow-derived mesenchymal stem cells are detected by monoclonal antibodies. Bone 1992;13:69-80.
Gang EJ, Hong SH, Jeong JA, Hwang SH, Kim SW, Yang IH, et al. In vitro mesengenic potential of human umbilical cord blood-derived mesenchymal stem cells. Biochem Bioph Res Co 2004;321:102-8.
Javazon EH, Beggs K, Flake A. Mesenchymal stem cells: paradoxes of passaging. Exp Hematol 2004;32:414-25.
Park PC, Selvarajah S, Bayani J, Zielenska M, Squire JA. Stem cell enrichment approaches. Semin Cancer Biol 2007;17:257-64.
Gudoitti JE, Bregerie O, Robert A, Debey P, Brechot C, Desdoutes C. Liver cell poliplooidization: a pivotal role for binuclear hepatocytes. J Biol Chem 2003;278:19095-101.
Alison MR, Pouslom R, Otto WR, Vig P, Brittan M. Recipies for adult stem cell plasticity:fusion cuisine or readymade. J Clin Pathol 2004;57:113-20.
Khoramroudi A, Nasiri S, Amiri I. Avaluating biochemical factors of in vitro differentiated hepatocyte like cells derived from cord blood stem cells. Armaghane Danesh 1998;3:23-34.[Persian].
Raufi A, Amini A, Azadbakht M, Aboozari M, Fathi F. In vitro differentiation of human umbilical vein mesenchymal stem cells into hepatocyte-like cells identified by cellular uptake of Indocyanine Green. blood 2010;7:33-40.[Persian].
Wright N, Samuelson L, Walkup MH, Chandrasekaran P, Gerber DA. Enreachment of a bipotent hepatic progenitor cell from native liver tissue. Biochem Biophys Res Commun 2008;36:367-72.
Khuu DN, Najimi M, Sokal EM. Epithelial cells with hepatobiliary phenotype: Is it another stem cell candidate for healthy adult human liver. World J Gastroenterol 2007;13:1554-60.
Kinoshita T, Miyajima A. Cytokine regulation of liver development. Biochim Biophys Acta 2002;1592:303-12.
Fujino H, Hiramatsu H, Tsuchiya A, Niwa A, Noma H, Shiota M, et al. Human cord blood cd34+ cells develop into hepatocytes in the livers of nod/scid/gc nnull mice through cell fusion. FASEB J 2007;21:3499-510.
Ek M, Soderdahl T, Kuppers-Munther B, Edsbagge J, Andersson TB, Bjorquist P, et al. Expression of drug metabolizing enzymesiin hepatocyte-like cells derived from human embryonic stem cells. Biochem Pharmacol 2007;74:496-503.
Ma N, Ladilov Y, Kaminski A, Piechaczek C, Choi YH, Li W, et al. Umbilical cord blood cell transplantation for myocardial regeneration. Transplant Proc 2006;38:771-3.
Sadat S, Gehmert S, Song YH, Yen Y, Bai X, Gaiser S, et al. The cardioprotective effect of mesenchymal stem cells is mediated by IGF-I and VEGF. Biochem Biophys Res Commun 2007;363:674-9.
Petersen BE BW, Mars WM, Patrene KD, Boggs SS, Sullivan AK. Bone marrow as a potential source for hepatic oval cells. Science 1999;248:1168-70.
Petersen BE. Hepatic "Stem" cells: coming full circle. Blood Cells Mol Dis 2001;27:590-600.
Almeida-Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED. Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood 2009;104:2582-90.
Hannoun Z, Filippi C, Sullivan G, Hay DC, Iredale JP. Hepatic endoderm differentiation from human embryonic stem cells. Current Stem Cell Research & Therapy 2010;5:233-44.
Onga SY, Daia H, Leong KW. Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture. Biomaterials 2006;27:4087-97.
Shiraki N, Umeda K, Sakashita N, Takeya M, Kume K, Kume S. Differentiation of mouse and human embryonic stem cells into hepatic lineages. Genes Cells 2008;13:731-46.
Tang XP, Zhang M, Yang X, Chen LM, Zeng Y. Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo and in vitro. World J Gastroenterol 2006;12:4014-9.
Hengstler JG, Brulport M, Schormann W, Bauer A, Hermes M, Nussler AK, et al. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol 2005;1:61-74.
Robertson JA. Human embryonic stem cell research: ethical and legal issues. Nat Rev Genet 2001;2:74-8.
Haven R, Lane D. Umbilical cord blood banking. J Obstet Gynecol India 2005;55:502-4.
Rubinstein P. Why cord blood. Hum Immunol 2006;67:398-404.
Knudtzon S. In vitro growth of granulocytic colonies from circulating cells in human cord blood. blood 1974;3:357-61.
Nanae F, Satoshi F, Takashi T, Junya T, Ida Kenji I, Hiroshi S, et al. Microencapsulated feeder cells as a source of soluble factors for expansion of cd34+ hematopoietic stem cells. Biomaterials 2007;28:4795-805.
Gluckman E BH, Auerbach AD, Friedman HS, Douglas GW, Devergie A, Esperou H, et al. Hematopoietic reconstitution in a patient with fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 1984;321:1174-8.
Liu CH, Hwang SM. Cytokine interactions in mesenchymal stem cells from cord blood. Cytokine 2005;32:270-9.
Nardi NB, SilvaMeirelles Ld. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol 2006;174:249-82.
Murphy JM FD, Hunziker EB. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004;36:568-84.
Kim YJ. Culture of umbilical cord- and cord blood-derived stem cells. Culture Of Human Stem Cells: John Wiley & Sons, Inc; 2007. p.156-86.
Kazemnejad S, Allameh A, Gharehbaghian A, Soleimani M, Amirizadeh N, Jazayeri M. Efficient replacing of fetal bovine serum with human platelet releasate during propagation and differentiation of human bone marrow-derived mesenchymal stem cells to functional hepatocytes-like cells. Vox Sang 2008;95:149-58.
Haynesworth SE, Baber MA, Caplan AI. Cell surface antigens on human bone marrow-derived mesenchymal stem cells are detected by monoclonal antibodies. Bone 1992;13:69-80.
Gang EJ, Hong SH, Jeong JA, Hwang SH, Kim SW, Yang IH, et al. In vitro mesengenic potential of human umbilical cord blood-derived mesenchymal stem cells. Biochem Bioph Res Co 2004;321:102-8.
Javazon EH, Beggs K, Flake A. Mesenchymal stem cells: paradoxes of passaging. Exp Hematol 2004;32:414-25.
Park PC, Selvarajah S, Bayani J, Zielenska M, Squire JA. Stem cell enrichment approaches. Semin Cancer Biol 2007;17:257-64.
Gudoitti JE, Bregerie O, Robert A, Debey P, Brechot C, Desdoutes C. Liver cell poliplooidization: a pivotal role for binuclear hepatocytes. J Biol Chem 2003;278:19095-101.
Alison MR, Pouslom R, Otto WR, Vig P, Brittan M. Recipies for adult stem cell plasticity:fusion cuisine or readymade. J Clin Pathol 2004;57:113-20.
Khoramroudi A, Nasiri S, Amiri I. Avaluating biochemical factors of in vitro differentiated hepatocyte like cells derived from cord blood stem cells. Armaghane Danesh 1998;3:23-34.[Persian].
Raufi A, Amini A, Azadbakht M, Aboozari M, Fathi F. In vitro differentiation of human umbilical vein mesenchymal stem cells into hepatocyte-like cells identified by cellular uptake of Indocyanine Green. blood 2010;7:33-40.[Persian].
Wright N, Samuelson L, Walkup MH, Chandrasekaran P, Gerber DA. Enreachment of a bipotent hepatic progenitor cell from native liver tissue. Biochem Biophys Res Commun 2008;36:367-72.
Khuu DN, Najimi M, Sokal EM. Epithelial cells with hepatobiliary phenotype: Is it another stem cell candidate for healthy adult human liver. World J Gastroenterol 2007;13:1554-60.
Kinoshita T, Miyajima A. Cytokine regulation of liver development. Biochim Biophys Acta 2002;1592:303-12.
Fujino H, Hiramatsu H, Tsuchiya A, Niwa A, Noma H, Shiota M, et al. Human cord blood cd34+ cells develop into hepatocytes in the livers of nod/scid/gc nnull mice through cell fusion. FASEB J 2007;21:3499-510.
Ek M, Soderdahl T, Kuppers-Munther B, Edsbagge J, Andersson TB, Bjorquist P, et al. Expression of drug metabolizing enzymesiin hepatocyte-like cells derived from human embryonic stem cells. Biochem Pharmacol 2007;74:496-503.
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