Hepatogenic differentiation of mesenchymal stem cells in a rat model of thioacetamide-induced liver cirrhosis

Shin Hwang, Hea Nam Hong, Hee Sung Kim, Se Ra Park, You Jin Won, Sang Tae Choi, Dongho Choi, Sung Gyu Lee

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Implantation of bone-marrow-derived MSCs (mesenchymal stem cells) has emerged as a potential treatment modality for liver failure, but in vivo differentiation of MSCs into functioning hepatocytes and its therapeutic effects have not yet been determined. We investigated MSC differentiation process in a rat model of TAA (thioacetamide)-induced liver cirrhosis. Male Sprague-Dawley rats were administered 0.04% TAA-containing water for 8 weeks, MSCs were injected into the spleen for transsplenic migration into the liver, and liver tissues were examined over 3 weeks. Ingestion of TAA for 8 weeks induced micronodular liver cirrhosis in 93% of rats. Injected MSCs were diffusely engrafted in the liver parenchyma, differentiated into CK19 (cytokeratin 19)- and thy1-positive oval cells and later into albumin-producing hepatocyte-like cells. MSC engraftment rate per slice was measured as 1.0-1.6%. MSC injection resulted in apoptosis of hepatic stellate cells and resultant resolution of fibrosis, but did not cause apoptosis of hepatocytes. Injection of MSCs treated with HGF (hepatocyte growth factor) in vitro for 2 weeks, which became CD90-negative and CK18-positive, resulted in chronological advancement of hepatogenic cellular differentiation by 2 weeks and decrease in anti-fibrotic activity. Early differentiation of MSCs to progenitor oval cells and hepatocytes results in various therapeutic effects, including repair of damaged hepatocytes, intracellular glycogen restoration and resolution of fibrosis. Thus, these results support that the in vivo hepatogenic differentiation of MSCs is related to the beneficial effects of MSCs rather than the differentiated hepatocytes themselves.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalCell Biology International
Volume36
Issue number3
DOIs
StatePublished - 2012 Mar 1

Fingerprint

Thioacetamide
Mesenchymal Stromal Cells
Liver Cirrhosis
Hepatocytes
Therapeutic Uses
Liver
Fibrosis
Apoptosis
Keratin-19
Hepatic Stellate Cells
Injections
Hepatocyte Growth Factor
Liver Failure
Glycogen
Sprague Dawley Rats
Cell Differentiation
Albumins
Stem Cells
Spleen
Eating

Keywords

  • Differentiation
  • Hepatocyte
  • Liver cirrhosis
  • Mesenchymal stem cell (MSC)
  • Rat Model
  • Thioacetamide (TAA)

Cite this

Hwang, S., Hong, H. N., Kim, H. S., Park, S. R., Won, Y. J., Choi, S. T., ... Lee, S. G. (2012). Hepatogenic differentiation of mesenchymal stem cells in a rat model of thioacetamide-induced liver cirrhosis. Cell Biology International, 36(3), 279-288. https://doi.org/10.1042/CBI20110325
Hwang, Shin ; Hong, Hea Nam ; Kim, Hee Sung ; Park, Se Ra ; Won, You Jin ; Choi, Sang Tae ; Choi, Dongho ; Lee, Sung Gyu. / Hepatogenic differentiation of mesenchymal stem cells in a rat model of thioacetamide-induced liver cirrhosis. In: Cell Biology International. 2012 ; Vol. 36, No. 3. pp. 279-288.
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Hepatogenic differentiation of mesenchymal stem cells in a rat model of thioacetamide-induced liver cirrhosis. / Hwang, Shin; Hong, Hea Nam; Kim, Hee Sung; Park, Se Ra; Won, You Jin; Choi, Sang Tae; Choi, Dongho; Lee, Sung Gyu.

In: Cell Biology International, Vol. 36, No. 3, 01.03.2012, p. 279-288.

Research output: Contribution to journalArticle

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AU - Hwang, Shin

AU - Hong, Hea Nam

AU - Kim, Hee Sung

AU - Park, Se Ra

AU - Won, You Jin

AU - Choi, Sang Tae

AU - Choi, Dongho

AU - Lee, Sung Gyu

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