Hepatic differentiation of liver-derived progenitor cells and their characterization by microRNA analysis

Yixin Chen, Hongchao Zhou, Aaron L. Sarver, Yan Zeng, Jayanta Roy-Chowdhury, Clifford J. Steer, M. Behnan Sahin

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We recently reported the isolation and characterization of a novel population of progenitor cells called liver-derived progenitor cells (LDPCs), which could differentiate into functional hepatocytes in vitro. However, our original studies resulted in relatively low and variable hepatic differentiation efficiency without validation of in vivo potential of LDPCs. Here, we report an efficient and robust hepatic differentiation of LDPCs under well-defined culture conditions and in vivo differentiation of LDPCs to mature hepatocytes. In addition to morphological studies, we performed reverse-transcription polymerase chain reaction (RT-PCR) and microRNA analyses of the in vitro hepatic differentiation of LDPCs to substantiate the efficiency of the differentiation process. The histological studies on the differentiated LDPCs showed that more than 50% of the cells were positive for albumin, cytokeratin 18, and hepatocyte nuclear factor 1α and contained glycogen particles, all consistent with differentiation to functional hepatocytes. We also demonstrated by RT-PCR that upon differentiation, they expressed several markers found in mature hepatocytes and the microRNA profile of LDPCs became similar to the profile of fresh hepatocytes, confirming our morphological findings. Finally, the transplantation of LDPCs in a dipeptidyl peptidase IV-deficient (DPPIV-/-) rat model showed that LDPCs were able to engraft and form mature hepatocytes in the livers of the DPPIV-/- rats. In summary, LDPCs are a unique population of liver progenitor cells capable of hepatic differentiation both in vitro and in vivo, which makes them a potentially valuable resource for important applications such as pharmacological studies and cell therapies for a variety of liver disorders.

Original languageEnglish (US)
Pages (from-to)1086-1097
Number of pages12
JournalLiver Transplantation
Volume16
Issue number9
DOIs
StatePublished - Sep 2010

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MicroRNAs
Stem Cells
Liver
Hepatocytes
Dipeptidyl Peptidase 4
Reverse Transcription
Hepatocyte Nuclear Factor 1
Keratin-18
Polymerase Chain Reaction
Cell- and Tissue-Based Therapy
Glycogen
Liver Transplantation
Population
Albumins

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

Cite this

Hepatic differentiation of liver-derived progenitor cells and their characterization by microRNA analysis. / Chen, Yixin; Zhou, Hongchao; Sarver, Aaron L.; Zeng, Yan; Roy-Chowdhury, Jayanta; Steer, Clifford J.; Sahin, M. Behnan.

In: Liver Transplantation, Vol. 16, No. 9, 09.2010, p. 1086-1097.

Research output: Contribution to journalArticle

Chen, Yixin ; Zhou, Hongchao ; Sarver, Aaron L. ; Zeng, Yan ; Roy-Chowdhury, Jayanta ; Steer, Clifford J. ; Sahin, M. Behnan. / Hepatic differentiation of liver-derived progenitor cells and their characterization by microRNA analysis. In: Liver Transplantation. 2010 ; Vol. 16, No. 9. pp. 1086-1097.
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