Human progenitor cells with high aldehyde dehydrogenase activity efficiently engraft into damaged liver in a nove model

Ping Zhou, Sara Hohm, Yetunde Olusanya, David A. Hess, Jan Nolta

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Human cord blood stem cells (hCBSCs) have been reported to generate hepatocyte-like cells and thus hold promise for repairing damaged liver. However, the frequency of hCBSC-derived hepatocytes varies tremendously between different studies, and it is still controversial as to whether hCBSC-derived cells can transdifferentiate into hepatocytes or simply fuse to recipient hepatocytes. We used the β-glucuronidase-deficient nonobese diabetic/severe combined immunodeficient mucopolysaccharidosis type VII (NOD/SCID/MPSVII) mouse model for better identification of engrafted cells.Wetransplanted lineage-depleted human umbilical cord blood-derived cells with high aldehyde dehydrogenase activity (ALDHhiLin-) into irradiated NOD/SCID/MPSVII mice followed by carbon tetrachloride administration to induced liver damage. ALDHhiLin- cells were efficiently engrafted in the recipient mouse livers and improved recovery of the mice from toxic insult. The percentage of human cells in these livers ranged between 3% and 14.2% using quantitative real-time polymerase chain reaction. Furthermore, human-originated cells expressing liver-specific α1-antitrypsin messenger RNA, albumin and hepatocyte nuclear factor 1 protein were detected in the recipient livers. Interestingly, human versus murine centromeric fluorescent in situ hybridization analysis on the liver sections demonstrated that most human cells were not fused to mouse cells. However, the majority of the human originated albumin-expressing cells also carried mouse genetic material, hence were the product of cell fusion. Conclusion: hCBSCs or their progeny may home to the injured liver and release trophic factors that hasten tissue repair, whereas fusion of these cells with hepatocytes may occur rarely and contribute to a lesser extent to liver repair.

Original languageEnglish (US)
Pages (from-to)1992-2000
Number of pages9
JournalHepatology
Volume49
Issue number6
DOIs
StatePublished - Jun 2009

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Aldehyde Dehydrogenase
Stem Cells
Liver
Fetal Blood
Hepatocytes
Blood Cells
Mucopolysaccharidosis VII
Cell Fusion
Albumins
Hepatocyte Nuclear Factor 1
Carbon Tetrachloride
Poisons
Glucuronidase
Thromboplastin
Fluorescence In Situ Hybridization
Real-Time Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Hepatology

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Human progenitor cells with high aldehyde dehydrogenase activity efficiently engraft into damaged liver in a nove model. / Zhou, Ping; Hohm, Sara; Olusanya, Yetunde; Hess, David A.; Nolta, Jan.

In: Hepatology, Vol. 49, No. 6, 06.2009, p. 1992-2000.

Research output: Contribution to journalArticle

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