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Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues.
J Gastroenterol Hepatol 2012; 27(8):1362-70JG

Abstract

BACKGROUND AND AIM

Although a liver transplantation is considered to be the only effective long-term treatment in many cases of liver diseases, it is limited by a lack of donor organs and immune rejection. As an autologous stem cell approach, this study was conducted to assess whether forkhead box A2 (Foxa2) gene overexpression in bone marrow-derived mesenchymal stem cells (MSC) could protect the liver from hepatic diseases by stimulating tissue regeneration after cell transplantation.

METHODS

Rat MSC (rMSC) were isolated, characterized, and induced to hepatocytes that expressed liver-specific markers. Four different treatments (control [phosphate-buffered saline], rMSC alone, rMSC/pIRES-enhanced green fluorescent protein (EGFP) vector, and rMSC/pIRES-EGFP/human Foxa2) were injected into the spleen of carbon tetrachloride-injured rats. Biochemical and histological analyses on days 30, 60, and 90 post-transplantation were performed to evaluate the therapeutic capacities of MSC overexpressing hFoxa2.

RESULTS

rMSC transfected with hFoxa2 were induced into hepatogenic linage and expressed several liver-specific genes, such as, Foxa2, α-fetoprotein, cytokeratin-18, hepatocyte nuclear factor-1α, and hepatocyte growth factor. A group of animals treated with MSC/hFoxa2 showed significant recovery of liver-specific enzyme expressions to normal levels at the end of the study (90 days). Furthermore, when compared to the fibrotic areas of the samples treated with MSC alone or MSC/vector, the fibrotic area of the samples treated with rMSC/hFoxa2 for 90 days significantly decreased, until they were completely gone.

CONCLUSIONS

Human Foxa2 efficiently promoted the incorporation of MSC into liver grafts, suggesting that hFoxa2 genes could be used for the structural or functional recovery of damaged liver cells.

Authors+Show Affiliations

Department of Biotechnology, Korea University, Seoul, Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22432472

Citation

Cho, Jong-Woo, et al. "Therapeutic Potential of Mesenchymal Stem Cells Overexpressing Human Forkhead Box A2 Gene in the Regeneration of Damaged Liver Tissues." Journal of Gastroenterology and Hepatology, vol. 27, no. 8, 2012, pp. 1362-70.
Cho JW, Lee CY, Ko Y. Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues. J Gastroenterol Hepatol. 2012;27(8):1362-70.
Cho, J. W., Lee, C. Y., & Ko, Y. (2012). Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues. Journal of Gastroenterology and Hepatology, 27(8), pp. 1362-70. doi:10.1111/j.1440-1746.2012.07137.x.
Cho JW, Lee CY, Ko Y. Therapeutic Potential of Mesenchymal Stem Cells Overexpressing Human Forkhead Box A2 Gene in the Regeneration of Damaged Liver Tissues. J Gastroenterol Hepatol. 2012;27(8):1362-70. PubMed PMID: 22432472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues. AU - Cho,Jong-Woo, AU - Lee,Chul-Young, AU - Ko,Yong, PY - 2012/3/22/entrez PY - 2012/3/22/pubmed PY - 2012/12/27/medline SP - 1362 EP - 70 JF - Journal of gastroenterology and hepatology JO - J. Gastroenterol. Hepatol. VL - 27 IS - 8 N2 - BACKGROUND AND AIM: Although a liver transplantation is considered to be the only effective long-term treatment in many cases of liver diseases, it is limited by a lack of donor organs and immune rejection. As an autologous stem cell approach, this study was conducted to assess whether forkhead box A2 (Foxa2) gene overexpression in bone marrow-derived mesenchymal stem cells (MSC) could protect the liver from hepatic diseases by stimulating tissue regeneration after cell transplantation. METHODS: Rat MSC (rMSC) were isolated, characterized, and induced to hepatocytes that expressed liver-specific markers. Four different treatments (control [phosphate-buffered saline], rMSC alone, rMSC/pIRES-enhanced green fluorescent protein (EGFP) vector, and rMSC/pIRES-EGFP/human Foxa2) were injected into the spleen of carbon tetrachloride-injured rats. Biochemical and histological analyses on days 30, 60, and 90 post-transplantation were performed to evaluate the therapeutic capacities of MSC overexpressing hFoxa2. RESULTS: rMSC transfected with hFoxa2 were induced into hepatogenic linage and expressed several liver-specific genes, such as, Foxa2, α-fetoprotein, cytokeratin-18, hepatocyte nuclear factor-1α, and hepatocyte growth factor. A group of animals treated with MSC/hFoxa2 showed significant recovery of liver-specific enzyme expressions to normal levels at the end of the study (90 days). Furthermore, when compared to the fibrotic areas of the samples treated with MSC alone or MSC/vector, the fibrotic area of the samples treated with rMSC/hFoxa2 for 90 days significantly decreased, until they were completely gone. CONCLUSIONS: Human Foxa2 efficiently promoted the incorporation of MSC into liver grafts, suggesting that hFoxa2 genes could be used for the structural or functional recovery of damaged liver cells. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/22432472/Therapeutic_potential_of_mesenchymal_stem_cells_overexpressing_human_forkhead_box_A2_gene_in_the_regeneration_of_damaged_liver_tissues_ L2 - https://doi.org/10.1111/j.1440-1746.2012.07137.x DB - PRIME DP - Unbound Medicine ER -