Hande KOCAK, Zeynep TOKCAER-KESKİN, Burcu İNSAL, İhsan GURSEL, Kamil Can AKÇALI

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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 yenilenmesi esnasında yenilenme potansiyelini arttırabildiklerini belirlemek için gerçekleştirilmiştir. Normal ve karaciğerleri kısmen çıkarılmış sıçanlar, sıçan kemik iliğinden elde edilip çoğaltılan mesenkimal kök hücreler ile muamele edilmişlerdir. Mesenkimal kök hücrelerin toplanması Eş Zamanlı Polimeraz Zincir Reaksiyonu (RT-PCR), Floresan Aktivite Hücre Ayırma (FACS), ve Immunfloresan Boyama (IFS) ile doğrulanmıştır. Sham ve karaciğeri kısmen alınmış sıçan grupları arasındaki farklılığın istatistiki analizinde Student's t-testi kullanılmıştır. Elde edilen sonuçlar mezenkimal kök hücrelerinde çeşitli TLR’lerin ifade edildiklerini ve bu hücrelerin yenilenme esnasında toplanmalarının meydana gelen hasarın zamanlamasına bağlı olduğunu göstermiştir. Normal sıçanların kemik iliğinden izole edilen mezenkimal kök hücreler hasarlı karaciğerde enjeksiyon sonrası 3. günde görülmüşlerdir. Hasarsız hayvanların karaciğer kesitlerinde işaretli bir mezenkimal kök hücre görülmemiştir. Mezenkimal kök hücre uygulaması TLR2, 3 ve 9'un ifadesinin anlamlı bir şekilde değiştirirken yenilenen karaciğere göç etme yeteneklerini devam ettirmişlerdir. Sonuçlar, karaciğer yenilenmesi esnasında mezenkimal kök hücre uygulamasının, hücrelerin uygulandığı hasarsız karaciğer parçalarında TLR’lerin ifadelerini değiştirme yoluyla immün yanıtı modüle ettiğini ortaya koymaktadır. TLR ifadesindeki bu değişim kısmı hepatoktemi sonrası yenilenme sürecine katkı sağlayabilir niteliktedir.

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.
Keywords:

Mesenchymal stem cell, TLR, homing, liver regeneration, rat,

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Trakya University Journal of Natural Sciences-Cover
  • ISSN: 2147-0294
  • Yayın Aralığı: Yılda 2 Sayı
  • Başlangıç: 2000
  • Yayıncı: Trakya Üniversitesi
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