Deneysel Sıçan Yüksek Dereceli Beyin Tümörü Modelinde İnsan Kaynaklı Mezenşimal Kök Hücre Göçünün İzlenmesi

Abstract

Objective Glioblastoma Multiforme (GBM) is one of the most malign tumors. Survival rates are too short and quality of life is poor after the diagnosis and the treatment. With radical surgery, chemotherapy and radiotherapy mean survival is 14 months. Due to the invasive and infiltrating pattern, GBM can spread to the whole brain. And Blood Brain Barrier prevents chemothereupatic agents reaching to the remainig tumor cells after the surgery. Mesenchymal stem cells (MSC) can migrate to injured tissues or tumor sites. This gave birth to an idea that they can be used as a vehichle in GBM treatment. The objective of this study is to create rat brain tumor model and to track MSCs migrating to the tumor. Method A number of 24 female, 200-240 gr., Wistar albino rats were used in this study. Rats were divided into five groups; control tumor (n=6), sham operation + MSC to the opposite hemisphere (n=3), sham operation + MSC to Cerebro Spine Fluid (CSF) (n=3), tumor + MSC to the opposite hemisphere (n=6) and tumor + MSC to CSF (n=6). RG2 rat glioma was enjected into the right hemispheres to rats in control tumor and tumor groups, whereares tumor medium was enjected into the right hemispheres to rats in sham groups. On day 9 , after prooving the tumor on the MRI, MSC with flourescence nanoparticles were injected into the left hemispheres or into the cisterna magna in either grıups. MSCs were also injected the hemisphere or into the cisterna magna in Sham grups as well. No MSCs were imjected to the control gruop. On day 14, another MRG scan was taken, tumor dimensions was calculated and rats were decapitated. Brains were examined under light microscopy and flourescence microscopy. vi Results Tumor masses were seen in control gruop. No MSC migration to the tumor medium injection site was seen in either sham groups; but one rat in sham hemisphere group showed local inflamation at MSC injection zone. We saw MSC migration and inflamatury response in all rats when MSCs we injected to the hemisphere. Inflamatuary response was also seen when MSCs were injected into cisterna magna but no MSC migration was seen in those rats. Conclusion With local injection, MSCs migrate to the tumor and start inflamatuary response. But no MSC migration was seen when injected into Cerebro Spinal Fluid (CSF), althought inflamatury response was present in those rats. This study showed that MSC can migrate to the tumor throught axonal pathways but MSCs can not pass the epandymal cells. Decreasing in the tumor mass due to the inflamation was seen, and the inflamation probably was caused by the mediators secreted by MSCs. Stem cells can be used as vectors when applied parachymally. The inflamatury response and tumor mass reduction is a new observetion and its planned to make additional studies to test it.