In Vitro Differentiation of Embryonic and Adult Stem Cells into Hepatocytes: State of the Art

Abstract

Stem cells are a unique source of self-renewing cells within the human body. Before the end of the last millennium, adult stem cells, in contrast to their embryonic counterparts, were considered to be lineage-restricted cells or incapable of crossing lineage boundaries. However, the unique breakthrough of muscle and liver regeneration by adult bone marrow stem cells at the end of the 1990s ended this long-standing paradigm. Since then, the number of articles reporting the existence of multipotent stem cells in skin, neuronal tissue, adipose tissue, and bone marrow has escalated, giving rise, both in vivo and in vitro, to cell types other than their tissue of origin. The phenomenon of fate reprogrammation and phenotypic diversification remains, though, an enigmatic and rare process. Understanding how to control both proliferation and differentiation of stem cells and their progeny is a challenge in many fields, going from preclinical drug discovery and development to clinical therapy. In this review, we focus on current strategies to differentiate embryonic, mesenchymal(-like), and liver stem/progenitor cells into hepatocytes in vitro. Special attention is paid to intracellular and extracellular signaling, genetic modification, and cell-cell and cell-matrix interactions. In addition, some recommendations are proposed to standardize, optimize, and enrich the in vitro production of hepatocyte-like cells out of stem/progenitor cells.

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106. 106.

     Pack R, Heck R, Dienes HP, et al. Isolation, biochemical characterization, long-term culture, and phenotype modulation of oval cells from carcinogen-fed rats. Exp Cell Res. 1993;204:198-209.

     Not in our library10.1006/excr.1993.1025

107. 107.

     Strick-Marchand H, Weiss MC. Inducible differentiation and morphogenesis of bipotential liver cell lines from wild-type mouse embryos. Hepatology. 2002;36:794-804.

     Not in our library10.1053/jhep.2002.36123

108. 108.

     Yamasaki C, Tateno C, Aratani A, et al. Growth and differentiation of colony-forming human hepatocytes in vitro. J Hepatol. 2006;44:749-757.

     Not in our library10.1016/j.jhep.2005.10.028

109. 109.

     Coleman WB, Smith GJ, Grisham JW. Development of dexamethasone-inducible tyrosine aminotransferase activity in WB-F344 rat liver epithelial stemlike cells cultured in the presence of sodium butyrate. J Cell Physiol. 1994;161:463-469.

     Not in our library10.1002/jcp.1041610309

110. 110.

     Ott M, Rajvanshi P, Sokhi RP, et al. Differentiation-specific regulation of transgene expression in a diploid epithelial cell line derived from the normal F344 rat liver. J Pathol. 1999;187:365-373.

     Not in our library10.1002/(sici)1096-9896(199902)187:3<365::aid-path237>3.0.co;2-z

111. 111.

     Li W, You P, Wei Q, et al. Hepatic differentiation and transcriptional profile of the mouse liver epithelial progenitor cells (LEPCs) under the induction of sodium butyrate. Front Biosci. 2007;12:1691-1698.

     Not in our library10.2741/2181

112. 112.

     Koch KS, Sell S, Leffert HL. Normal liver progenitor cells in culture. Stem Cells Handbook. 2004;367-384.

     Not in our library

113. 113.

     Cerec V, Glaise D, Garnier D, et al. Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor. Hepatology. 2007;45:957-967.

     Not in our library10.1002/hep.21536

114. 114.

     He NH, Zhao WL, Wang YM. Human fetal liver nonparenchymal mesenchymal stem cells differentiate into functional hepatocyte-like cells in vitro. Zhonghua Gan Zang Bing Za Zhi. 2007;15:164-169.

     Not in our library

115. 115.

     Vogel WH, Boehme DH, Salerno NJ. Activities of tyrosine aminotransferase in various human tissues. J Neurochem. 1973;21:705-707.

     Not in our library10.1111/j.1471-4159.1973.tb06016.x

116. 116.

     Yánez AJ, Nualart F, Droppelmann C, et al. Broad expression of fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase provide evidence for gluconeogenesis in human tissues other than liver and kidney. J Cell Physiol. 2003;197:189-197.

     Not in our library10.1002/jcp.10337

117. 117.

     Ogasawara K, Terada T, Asaka JI, et al. Hepatocyte nuclear factor-4α regulates the human organic anion transporter 1 gene in the kidney. Am J Physiol Renal Physiol. 2007;292:F1819-F1826.

     Not in our library10.1152/ajprenal.00017.2007

118. 118.

     Gu N, Adachi T, Matsunaga T, et al. HNF-1α participates in glucose regulation of sucrase-isomaltase gene expression in epithelial intestinal cells. Biochem Biophys Res Commun. 2007;353:617-622.

     Not in our library10.1016/j.bbrc.2006.12.065

119. 119.

     Ihara A, Yamagata K, Nammo T, et al. Functional characterization of the HNF4α isoform (HNF4α8) expressed in pancreatic β-cells. Biochem Biophys Res Commun. 2005;329:984-990.

     Not in our library10.1016/j.bbrc.2005.02.072

120. 120.

     Martis PC, Whitsett JA, Xu Y, et al. C/EBPα is required for lung maturation at birth. Development. 2006;133:1155-1164.

     Not in our library10.1242/dev.02273

121. 121.

     Dziadek M, Adamson E. Localization and synthesis of α-foetoprotein in post-implantation mouse embryos. J Embryol Exp Morphol. 1978;43:289-313.

     Not in our library

122. 122.

     Gulbis B, Jauniaux E, Cotton F, et al. Protein and enzyme patterns in the fluid cavities of the first trimester gestational sac: relevance to the absorptive role of secondary yolk sac. Mol Hum Reprod. 1998;4:857-862.

     Not in our library10.1093/molehr/4.9.857

123. 123.

     Gómez-Lechón MJ, Donato MT, Castell JV, et al. Human hepatocytes in primary culture: the choice to investigate drug metabolism in man. Curr Drug Metab. 2004;5:443-462.

     Not in our library10.2174/1389200043335414

124. 124.

     Kmieć Z. Cooperation of liver cells in health and disease. Adv Anat Embryol Cell Biol. 2001;161(III-XIII):1-151.

     Not in our library10.1007/978-3-642-56553-3

125. 125.

     Cascio S, Zaret KS. Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation. Development. 1991;113:217-225.

     Not in our library10.1242/dev.113.1.217

126. 126.

     Shiojiri N. Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse. J Embryol Exp Morphol. 1981;62:139-152.

     Not in our library

127. 127.

     Rozga J. Liver support technology—an update. Xenotransplantation. 2006;13:380-389.

     Not in our library10.1111/j.1399-3089.2006.00323.x

128. 128.

     Brulport M, Schormann W, Bauer A, et al. Fate of extrahepatic human stem and precursor cells after transplantation into mouse livers. Hepatology. 2007;46:861-870.

     Not in our library10.1002/hep.21745

129. 129.

     Hengstler JG, Brulport M, Schormann W, et al. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol. 2005;1:61-74.

     Not in our library10.1517/17425255.1.1.61

130. 130.

     Meuleman P, Libbrecht L, De VR, et al. Morphological and biochemical characterization of a human liver in a uPA-SCID mouse chimera. Hepatology. 2005;41:847-856.

     Not in our library10.1002/hep.20657

131. 131.

     Pearson H. Stem-cell tagging shows flaws. Nature. 2006;439:519.

     Not in our library10.1038/439519a

132. 132.

     Sathananthan AH, Trounson A. Human embryonic stem cells and their spontaneous differentiation. Ital J Anat Embryol. 2005;110:151-157.

     Not in our library

133. 133.

     Lavon N, Benvenisty N. Study of hepatocyte differentiation using embryonic stem cells. J Cell Biochem. 2005;96:1193-1202.

     Not in our library10.1002/jcb.20590

134. 134.

     Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001;19:193-204.

     Not in our library10.1634/stemcells.19-3-193

135. 135.

     Amano T, Gertsenstein M, Nagy A, et al. Nuclear transfer reprogramming does not improve the low developmental potency of embryonic stem cells induced by long-term culture. Reproduction. 2006;132:257-263.

     Not in our library10.1530/rep.1.01117

136. 136.

     Nierhoff D, Ogawa A, Oertel M, et al. Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Hepatology. 2005;42:130-139.

     Not in our library10.1002/hep.20735

137. 137.

     Nowak G, Ericzon BG, Nava S, et al. Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo. Gut. 2005;54:972-979.

     Not in our library10.1136/gut.2005.064477

138. 138.

     Kang XQ, Zang WJ, Song TS, et al. Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro. World J Gastroenterol. 2005;11:3479-3484.

     Not in our library10.3748/wjg.v11.i22.3479

139. 139.

     Kwak DH, Yu K, Kim SM, et al. Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells. Exp Mol Med. 2006;38:668-676.

     Not in our library10.1038/emm.2006.79

140. 140.

     Park KS, Lee YS, Kang KS. In vitro neuronal and osteogenic differentiation of mesenchymal stem cells from human umbilical cord blood. J Vet Sci. 2006;7:343-348.

     Not in our library10.4142/jvs.2006.7.4.343

141. 141.

     Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006;5:91-116.

     Not in our library10.1016/j.arr.2005.10.001

142. 142.

     Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H, Ochiya T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 2007;46:219-228.

     Not in our library10.1002/hep.21704

143. 143.

     Lysy PA, Campard D, Smets F, et al. Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells. Cell Prolif. 2008;41:36-58.

     Not in our library10.1111/j.1365-2184.2007.00507.x

144. 144.

     Tarnowski M, Koryciak-Komarska H, Czekaj P, et al. The comparison of multipotential for differentiation of progenitor mesenchymal-like stem cells obtained from livers of young and old rats. Folia Histochem Cytobiol. 2007;45:245-254.

     Not in our library

145. 145.

     Yamamoto Y, Banas A, Murata S, et al. A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells. FEBS J. 2008;275:1260-1273.

     Not in our library10.1111/j.1742-4658.2008.06287.x

146. 146.

     Bobis S, Jarocha D, Majka M. Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol. 2006;44:215-230.

     Not in our library

147. 147.

     Digirolamo CM, Stokes D, Colter D, et al. Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol. 1999;107:275-281.

     Not in our library10.1046/j.1365-2141.1999.01715.x

148. 148.

     Beyer NN, da Silva ML. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol. 2006;249-282.

     Not in our library

149. 149.

     Phinney DG, Kopen G, Isaacson RL, et al. 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.

     Not in our library

150. 150.

     Phinney DG, Kopen G, Righter W, et al. Donor variation in the growth properties and osteogenic potential of human marrow stromal cells. J Cell Biochem. 1999;75:424-436.

     Not in our library

151. 151.

     Simmons PJ, Masinovsky B, Longenecker BM, et al. Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood. 1992;80:388-395.

     Not in our library

152. 152.

     Theise ND, Harris R. Postmodern biology: (adult) (stem) cells are plastic, stochastic, complex, and uncertain. Handb Exp Pharmacol. 2006;389-408.

     Not in our library

153. 153.

     Pansky A, Roitzheim B, Tobiasch E. Differentiation potential of adult human mesenchymal stem cells. Clin Lab. 2007;53:81-84.

     Not in our library

154. 154.

     Wagner W, Wein F, Seckinger A, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 2005;33:1402-1416.

     Not in our library10.1016/j.exphem.2005.07.003

155. 155.

     Papeleu P, Loyer P, Vanhaecke T, et al. Trichostatin A induces differential cell cycle arrests but does not induce apoptosis in primary cultures of mitogen-stimulated rat hepatocytes. J Hepatol. 2003;39:374-382.

     Not in our library10.1016/s0168-8278(03)00288-5

156. 156.

     Papeleu P, Vanhaecke T, Elaut G, et al. Differential effects of histone deacetylase inhibitors in tumor and normal cells—what is the toxicological relevance? Crit Rev Toxicol. 2005;35:363-378.

     Not in our library10.1080/10408440590935639

157. 157.

     Herold C, Ganslmayer M, Ocker M, et al. The histone-deacetylase inhibitor trichostatin A blocks proliferation and triggers apoptotic programs in hepatoma cells. J Hepatol. 2002;36:233-240.

     Not in our library10.1016/s0168-8278(01)00257-4

158. 158.

     Vanhaecke T, Papeleu P, Elaut G, et al. Trichostatin A-like hydroxamate histone deacetylase inhibitors as therapeutic agents: toxicological point of view. Curr Med Chem. 2004;11:1629-1643.

     Not in our library10.2174/0929867043365099

159. 159.

     Henkens T, Papeleu P, Elaut G, et al. Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes. Toxicol Appl Pharmacol. 2007;218:64-71.

     Not in our library10.1016/j.taap.2006.10.012

160. 160.

     Cerny J, Quesenberry PJ. Chromatin remodeling and stem cell theory of relativity. J Cell Physiol. 2004;201:1-16.

     Not in our library10.1002/jcp.20071

161. 161.

     Shahbazian MD, Grunstein M. Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem. 2007;76:75-100.

     Not in our library10.1146/annurev.biochem.76.052705.162114

162. 162.

     Hsieh J, Nakashima K, Kuwabara T, et al. Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci U|S|A. 2004;101:16659-16664.

     Not in our library10.1073/pnas.0407643101

163. 163.

     Shen S, Li J, Casaccia-Bonnefil P. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J Cell Biol. 2005;169:577-589.

     Not in our library10.1083/jcb.200412101

164. 164.

     Rössig L, Urbich C, Bruhl T, et al. Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells. J Exp Med. 2005;201:1825-1835.

     Not in our library10.1084/jem.20042097

165. 165.

     Terranova R, Sauer S, Merkenschlager M, et al. The reorganisation of constitutive heterochromatin in differentiating muscle requires HDAC activity. Exp Cell Res. 2005;310:344-356.

     Not in our library10.1016/j.yexcr.2005.07.031

166. 166.

     Derynck R, Wagner EF. Cell differentiation. Curr Opin Cell Biol. 1995;7:843-844.

     Not in our library10.1016/0955-0674(95)80068-9

167. 167.

     Elaut G, Henkens T, Papeleu P, et al. Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures. Curr Drug Metab. 2006;7:629-660.

     Not in our library10.2174/138920006778017759

168. 168.

     Elaut G, Torok G, Vinken M, et al. Major phase I biotransformation pathways of trichostatin a in rat hepatocytes and in rat and human liver microsomes. Drug Metab Dispos. 2002;30:1320-1328.

     Not in our library10.1124/dmd.30.12.1320

169. 169.

     Elaut G, Laus G, Alexandre E, et al. A metabolic screening study of trichostatin A (TSA) and TSA-like histone deacetylase inhibitors in rat and human primary hepatocyte cultures. J Pharmacol Exp Ther. 2007;321:400-408.

     Not in our library10.1124/jpet.106.116202

170. 170.

     Miura M, Miura Y, Padilla-Nash HM, et al. Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells. 2006;24:1095-1103.

     Not in our library10.1634/stemcells.2005-0403

171. 171.
     Aging of mesenchymal stem cell in vitro · 2006

     No notice
172. 172.

     Rubio D, Garcia-Castro J, Martin MC, et al. Spontaneous human adult stem cell transformation. Cancer Res. 2005;65:3035-3039.

     Not in our library10.1158/0008-5472.can-04-4194

173. 173.

     Neildez-Nguyen TM, Parisot A, Vignal C, et al. Epigenetic gene expression noise and phenotypic diversification of clonal cell populations. Differentiation. 2008;76:33-40.

     Not in our library10.1111/j.1432-0436.2007.00219.x

174. 174.

     Fehrer C, Laschober G, Lepperdinger G. Aging of murine mesenchymal stem cells. Ann N|Y Acad Sci. 2006;1067:235-242.

     Not in our library10.1196/annals.1354.030

175. 175.

     Baharvand H, Hashemi SM, Kazemi AS, et al. Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. Int J Dev Biol. 2006;50:645-652.

     Not in our library10.1387/ijdb.052072hb

176. 176.

     Meng Y, Huang SL, Min J, et al. E14 mouse embryonic stem cells differentiate into hepatocyt ESC. Zhonghua Gan Zang Bing Za Zhi. 2004;12:714-717.

     Not in our library

177. 177.

     Kulkarni JS, Khanna A. Functional hepatocyte-like cells derived from mouse embryonic stem cells: a novel in vitro hepatotoxicity model for drug screening. Toxicol In Vitro. 2006;20:1014-1022.

     Not in our library10.1016/j.tiv.2005.12.011

178. 178.

     Hu AB, He XS, Cai JY, et al. Hepatic differentiation of mouse ES cells into BE cells in vitro. Cell Biol Int. 2006;30:459-465.

     Not in our library10.1016/j.cellbi.2006.01.006

179. 179.

     Teratani T, Yamamoto H, Aoyagi K, et al. Direct hepatic fate specification from mouse embryonic stem cells. Hepatology. 2005;41:836-846.

     Not in our library10.1002/hep.20629

180. 180.

     Gouon-Evans V, Boussemart L, Gadue P, et al. BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nat Biotechnol. 2006;24:1402-1411.

     Not in our library10.1038/nbt1258

181. 181.

     Pan YL, Cai JY, Hu AB. Differentiation of hepatocytes from mouse embryonic stem cells and its significance. Hepatobiliary Pancreat Dis Int. 2005;4:291-294.

     Not in our library

182. 182.

     Tomizawa M, Toyama Y, Ito C, et al. Hepatoblast-like cells enriched from mouse embryonic stem cells in medium without glucose, pyruvate, arginine, and tyrosine. Cell Tissue Res. 2008;333:17-27.

     Not in our library10.1007/s00441-008-0618-4

183. 183.

     Soto-Gutierrez A, Navarro-Alvarez N, Rivas-Carrillo JD, et al. Differentiation of human embryonic stem cells to hepatocytes using deleted variant of HGF and poly-amino-urethane-coated nonwoven polytetrafluoroethylene fabric. Cell Transplant. 2006;15:335-341.

     Not in our library10.3727/000000006783981945

184. 184.

     Li L, Sharma N, Chippada U, et al. Functional modulation of ES-derived hepatocyte lineage cells via substrate compliance alteration. Ann Biomed Eng. 2008;36:865-876.

     Not in our library10.1007/s10439-008-9458-3

185. 185.

     Mizumoto H, Aoki K, Nakazawa K, et al. Hepatic differentiation of embryonic stem cells in HF/organoid culture. Transplant Proc. 2008;40:611-613.

     Not in our library10.1016/j.transproceed.2008.01.023

186. 186.

     Maguire T, Novik E, Schloss R. Alginate-PLL microencapsulation: effect on the differentiation of embryonic stem cells into hepatocytes. Biotechnol Bioeng. 2006;93:581-591.

     Not in our library10.1002/bit.20748

187. 187.

     Chien CC, Yen BL, Lee FK, et al. In vitro differentiation of human placenta-derived multipotent cells into hepatocyte-like cells. Stem Cells. 2006;24:1759-1768.

     Not in our library10.1634/stemcells.2005-0521

188. 188.

     Kazemnejad S, Allameh A, Gharehbaghian A, et al. 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;95:149-158.

     Not in our library10.1111/j.1423-0410.2008.01075.x

189. 189.

     Campard D, Lysy PA, Najimi M, et al. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008;134:833-848.

     Not in our library10.1053/j.gastro.2007.12.024

190. 190.

     Shi XL, Mao L, Xu BY, et al. Optimization of an effective directed differentiation medium for differentiating mouse bone marrow mesenchymal stem cells into hepatocytes in vitro. Cell Biol Int. 2008;32:959-965.

     Not in our library10.1016/j.cellbi.2008.04.013

191. 191.

     Ke Z, Zhou F, Wang L, et al. Down-regulation of Wnt signaling could promote bone marrow-derived mesenchymal stem cells to differentiate into hepatocytes. Biochem Biophys Res Commun. 2008;367:342-348.

     Not in our library10.1016/j.bbrc.2007.12.134

192. 192.

     Chen Y, Dong XJ, Zhang GR, et al. In vitro differentiation of mouse bone marrow stromal stem cells into hepatocytes induced by conditioned culture medium of hepatocytes. J Cell Biochem. 2007;102:52-63.

     Not in our library10.1002/jcb.21275

193. 193.

     Yin L, Sun M, Ilic Z, et al. Derivation, characterization, and phenotypic variation of hepatic progenitor cell lines isolated from adult rats. Hepatology. 2002;35:315-324.

     Not in our library10.1053/jhep.2002.31355

194. 194.

     Jensen CH, Jauho EI, Santoni-Rugiu E, et al. Transit-amplifying ductular (oval) cells and their hepatocytic progeny are characterized by a novel and distinctive expression of delta-like protein/preadipocyte factor 1/fetal antigen 1. Am J Pathol. 2004;164:1347-1359.

     Not in our library10.1016/s0002-9440(10)63221-x

195. 195.

     Suzuki A, Iwama A, Miyashita H, et al. Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development. 2003;130:2513-2524.

     Not in our library10.1242/dev.00459

196. 196.

     Hussain SZ, Strom SC, Kirby MR, et al. Side population cells derived from adult human liver generate hepatocyte-like cells in vitro. Dig Dis Sci. 2005;50:1755-1763.

     Not in our library10.1007/s10620-005-2933-x

197. 197.

     Herrera MB, Bruno S, Buttiglieri S, et al. Isolation and characterization of a stem cell population from adult human liver. Stem Cells. 2006;24:2840-2850.

     Not in our library10.1634/stemcells.2006-0114

198. 198.

     Isabel Z, Miri B, Einav H, et al. Isolation, characterization and culture of Thy1-positive cells from fetal rat livers. World J Gastroenterol. 2006;12:3841-3847.

     Not in our library10.3748/wjg.v12.i24.3841

Cited by papers we hold 4

• Modeling the human placental barrier to understand Toxoplasma gondii´s vertical transmission · 2023
  Not checked
• Applications of Nanobiomaterials in the Therapy and Imaging of Acute Liver Failure · 2020
  Not checked
• Organotypic liver culture models: Meeting current challenges in toxicity testing · 2012
  No notice
• Mesenchymal Stem Cells in Renal Function Recovery after Acute Kidney Injury: Use of a Differentiating Agent in a Rat Model · 2011
  Not checked

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