Open Access

Hybrid cells differentiate to hepatic lineage cells and repair oxidative damage

  • Dan Xu1,
  • Feng Wang1Email author,
  • Hongyan Gu2,
  • Jia Wang2,
  • Qinglong Guo2,
  • Yanli Zhang1 and
  • Ziyu Wang1
Cellular & Molecular Biology LettersAn International Journal201015:18

DOI: 10.2478/s11658-010-0018-0

Received: 13 October 2009

Accepted: 26 May 2010

Published: 17 June 2010

Abstract

Hybrid cells derived from stem cells play an important role in organogenesis, tissue regeneration and cancer formation. However, the fate of hybrid cells and their range of function are poorly understood. Fusing stem cells and somatic cells induces somatic cell reprogramming, and the resulting hybrid cells are embryonic stem cell-like cells. Therefore, we hypothesize that fusion-induced hybrid cells may behave like ES cells in certain microenvironments. In this study, human hepatic cells were induced to apoptosis with H2O2, and then co-cultured with hybrid cells that had been derived from mouse ES cells and human hepatic cells using a transwell. After co-culturing, the degree of apoptosis was evaluated using Annexin-V/PI double-staining analysis, flow cytometry and Western-blot. We observed that H2O2-induced cell apoptosis was inhibited by co-culture. In addition, the activity of injury-related enzymes (GSH-Px, LDH and SOD) and the level of albumin release in the co-culture system trended toward the level of normal undamaged hepatic cells. The stably increased levels of secretion of ALB in the co-culture system also confirmed that co-culture with hybrid cells helped in recovery from injury. The fate of the hybrid cells was studied by analyzing their gene expression and protein expression profiles. The results of RT-PCR indicated that during co-culturing, like ES cells, hybrid cells differentiated into hepatic lineage cells. Hybrid cells transcripted genes from both parental cell genomes. Via immunocytochemical analysis, hepatic directional differentiation of the hybrid cells was also confirmed. After injecting the hybrid cells into the mouse liver, the GFP-labeled transplanted cells were distributed in the hepatic lobules and engrafted into the liver structure. This research expands the knowledge of fusion-related events and the possible function of hybrid cells. Moreover, it could indicate a new route of differentiation from pluripotent cells to tissue-specific cells via conditional co-culture.

Key words

Hybrid cells Regeneration Embryonic stem cell Differentiation Oxidative damage Apoptosis

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