PMID- 26540984 OWN - NLM STAT- MEDLINE DCOM- 20160712 LR - 20181202 IS - 1002-1892 (Print) IS - 1002-1892 (Linking) VI - 29 IP - 7 DP - 2015 Jul TI - [DIFFERENTIATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS INTO HEPATOCYTES INDUCED BY RAT FIBROTIC LIVER TISSUE EXTRACTS]. PG - 878-83 AB - OBJECTIVE: To investigate the differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes induced by rat fibrotic liver tissue extracts. METHODS: Liver fibrosis was induced in the Sprague Dawley rats (weighting, 180-220 g) by repeated intraperitoneal injections of 3% thioacetamide-saline at a dose of 200 mg/kg twice a week for 4 weeks; fibrotic liver tissues were used to prepare liver homogenate supernatants. The HUCMSCs at passage 3 were cultured in DMEM/F12 with 10% fetal bovine serum (FBS) (control group) and in DMEM/F12 with 10% FBS and 50 g/L liver homogenate supernatants (experimental group) for 7 days. The morphological changes of the cells were recorded; the protein levels of cytokeratin 18 (CK18), alpha fetoprotein (AFP), and CYP3A4 were measured using Western blot. The glycogen storing ability of the cells was detected by periodic acid-schiff (PAS) staining. Furthermore, the synthesis of albumin (ALB) and blood urea nitrogen (BUN) was measured. RESULTS: In experimental group, after 1 day of induction, the stem cells of fusiform shape began to lose sharp edges and progressively shrunk, and then they changed into hepatocyte-like cells with round and irregular shape at 7 days. Positive expressions of AFP, CK18, and CYP3A4 were observed in the experimental group, but negative expression in the control group. The concentrations of BUN and ALB were (0.43 +/- 0.07) mmol/L and (8.08 +/- 0.41) microg/mL in the control group and were (2.52 +/- 0.20) mmol/L and (41.48 +/- 4.11) microg/mL in the experimental group, showing significant differences (t=24.160, P = 0.000; t = 19.810, P = 0.000). PAS staining results showed navy blue nucleus and lavender cytoplasm in the control group, but dark purple cell body and visible nucleus in the experimental group. CONCLUSION: HUCMSCs could differentiate into hepatocyte-like cells induced by rat fibrotic liver tissue extracts, which have hepatocyte biomarkers (AFP, CK18, and CYP3A4) and hepatocyte-specific functions of glycogen storage, urea production and ALB secretion, so they could partially replace the function of hepatocytes, that may be one of the therapeutic mechanisms of stem cell transplantation. FAU - Yan, Cheng AU - Yan C FAU - Xue, Gai AU - Xue G FAU - Wu, Liying AU - Wu L FAU - Liu, Jianfang AU - Liu J FAU - Hou, Yanning AU - Hou Y LA - chi PT - Journal Article PL - China TA - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi JT - Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery JID - 9425194 RN - 0 (Keratin-18) RN - 0 (Liver Extracts) RN - 0 (Tissue Extracts) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Animals MH - Cell Differentiation/*drug effects/physiology MH - Cells, Cultured MH - Cord Blood Stem Cell Transplantation MH - Fetal Blood/*cytology MH - Hepatocyte Growth Factor/*pharmacology MH - Hepatocytes/*cytology/drug effects/metabolism MH - Humans MH - Keratin-18/biosynthesis MH - Liver/embryology MH - Liver Extracts/*pharmacology MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Stem Cells/cytology/drug effects MH - Tissue Extracts EDAT- 2015/11/07 06:00 MHDA- 2016/07/13 06:00 CRDT- 2015/11/07 06:00 PHST- 2015/11/07 06:00 [entrez] PHST- 2015/11/07 06:00 [pubmed] PHST- 2016/07/13 06:00 [medline] PST - ppublish SO - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015 Jul;29(7):878-83.