ADMINISTRATION OF BONE MARROW DERIVED MESENCHYMAL STEM CELLS MODULATE TLR EXPRESSION DURING LIVER REGENERATION

Liver cell transplantation is a powerful alternative to orthotopic cell transplantation in the treatment of liver failures. Recently, considerable effort is being channeled to understand the nature and kinetics of directing stem cells to effectively accumulate at the regenerating liver site. Mesenchymal stem cells are one of the promising cell sources modulating liver regeneration process. Present was designed to study how mesenchymal stem cells might modulate liver immune behaviors by changing Toll-like receptor (TLR) expression and increase regenerative potential during liver regeneration in rats. Normal and partially hepatectomized rats were treated with mesenchymal stem cells isolated and expanded from rat bone marrows. Accumulation of mesenchymal stem cells was confirmed by Real Time-Polymerase Chain Reaction (RT-PCR), Fluorescence-Activated Cell Sorting (FACS), and Immunofluorescence Staining (IFS). Student's t-test analysis was used to evaluate the significance of differences between sham and partially hepatectomized rat groups. Our results showed that mesenchymal stem cells expressed several TLRs, and their accumulation during regeneration was depended on the timing of injury. Mesenchymal stem cells isolated from bone marrow of normal rats were observed at the injured liver 3 days after the injection. There were no labeled mesenchymal stem cells in the liver sections of the uninjured animals. Mesenchymal stem cell administration significantly altered the expression of TLR2, 3 and 9 while retaining their migration potential to regenerating liver. Our findings implicated that mesenchymal stem cell administration during liver regeneration modulate the immune response through changing the expression of the TLRs in the remaining liver parts into which the cells are recruited or infused. This alteration may contribute to the regeneration process following partial hepatectomy. Karaciğer hücresi nakli, karaciğer yetmezliğinde ortotopik hücre nakline güçlü bir alternatiftir. Son yıllarda, kök hücrelerin doğalarının, kinetiklerinin ve yenilenen karaciğer bölgesinde etkili bir şekilde toplanmalarının sağlanmasının anlaşılması için hatırı sayılır gayretler sarf edilmektedir. Mesenkimal kök hücreler karaciğer yenilenme sürecini modüle eden ümit verici hücre kaynaklarından bir tanesidir. Bu çalışma, mezenkimal kök hücrelerin sıçanlarda toll benzeri reseptör (TLR) ifadesini değiştirmek suretiyle karaciğer immün yanıtını nasıl etkileyebildiklerini ve karaciğer