Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats

Rujun Zhai, Yongchun Wang, Le Qi, George Melville Williams, Bin Gao, Guang Song, James F. Burdick, Zhao Li Sun

Research output: Contribution to journalArticle

Abstract

Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low-dose FK506 (F). Here we show that AF combination therapy significantly increased lineage negative (Lin-) CD34+ and Lin-CD133+ stem cells in peripheral blood and enhanced recruitment of CD133+ cells into the remnant liver in a rat model of 85% partial hepatectomy. Recruiting CD133+ stem cells in the remnant liver was associated with increased proliferation of hepatic oval cells and paralleled the increased SDF-1, CXCR4 and HGF expression. Importantly, AF combination therapy increased the number of Ki67 positive hepatocytes and BrdU incorporation in the remnant liver and improved serum levels of albumin. Our results demonstrate that pharmacological mobilization of endogenous bone marrow stem cells with AF combination therapy can enhance endogenous stem cell mobilization to promote liver regeneration and improve liver function after extensive hepatectomy.

Original languageEnglish (US)
Article number3587
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Liver Regeneration
Bone Marrow Cells
Stem Cells
Pharmacology
Liver
Hepatectomy
Hepatocytes
Hematopoietic Stem Cell Mobilization
Liver Failure
Tacrolimus
Bromodeoxyuridine
Cell- and Tissue-Based Therapy
Serum Albumin
Therapeutics
Bone Marrow

ASJC Scopus subject areas

  • General

Cite this

Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats. / Zhai, Rujun; Wang, Yongchun; Qi, Le; Williams, George Melville; Gao, Bin; Song, Guang; Burdick, James F.; Sun, Zhao Li.

In: Scientific Reports, Vol. 8, No. 1, 3587, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Burdick, James F.

AU - Sun, Zhao Li

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