Karaciğer rejenerasyonu: Mezenkimal kök hücre ve toll benzeri reseptörlerin potansiyel rolleri

Liver has unique capacity to regenerate in response to loss of hepatocytes depending on viral infections, toxic reactions and cancer formation. Although liver regeneration have been extensively studied, factors participate in the process are still under extensive investigation. Differentiation and immunosuppressive potential, as well as homing capacity to the site of injury of mesenchymal stem cells (MSCs) can be harnessed in liver regeneration. Moreover, toll like receptors (TLRs) which are known to involve immuneregulatory mechanisms of MSCs may also be a player in this process. Therefore, in this study, our aim was to understand the possible roles of MSCs and TLRs during liver regeneration. First, TLR message distribution upon partial hepatectomy induction was assessed. Then, homing capacity of MSCs in liver regeneration was examined by injecting labeled MSC generated from normal or already PH initiated rats back into partially hepatectomized (PH) rats. After investigating MSC homing, mRNA expression profiles of several key TLRs in the course of liver regeneration with or without MSC administration was examined. Finally, the role of TLRs in immunoregulatory properties of MSCs was explored. Our data showed that MSCs from normal rats and at day 1 post PH are localized in liver of PH generated animals. We have also determined that injected MSCs increased TLR2, 3 and 9 expressions in livers in comparison to that of hepatectomized liver that did not receive any MSC injection. Therefore, our data suggests that during liver regeneration at post PH day 3, homing of MSCs to the site of injury is at maximum and TLRs do not play any roles in recruiting these cells to liver, but rather localized MSCs either cis or at trans manner promote TLR expression. Despite the fact that MSCs are known to be non-immunogenic, in the present study isolated MSCs from BM are found to be expressing a panel of TLR mRNAs and our findings strongly implicate that these TLRs are functional in terms of cytokine secretion upon triggered by their proper ligands. Finally, we have identified that mouse MSC possesses different levels of critical surface markers such as CD11b, CD45, CD90 and CD117 at different passages and led us to think that either sub-populations or contaminating cell fractions may exist within the studied MSC population and furthermore may contribute to stimulatory potential of MSCs.