Long-Term Influence of Bone Marrow-Derived Mesenchymal Stem Cells on Liver Ischemia-Reperfusion Injury in a Rat Model
Maciej Nowacki, Łukasz Nazarewski, Marta Pokrywczyńska, Tomasz Kloskowski, Dominik Tyloch, Katarzyna Pietkun, Arkadiusz Jundziłł, Marta Rasmus, Karolina Warda, Maciej Gagat, Alina Grzanka, Magdalena Bodnar, Andrzej Marszałek, Marek Krawczyk, Samy L. Habib, Tomasz Drewa
Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland
Ann Transplant 2015; 20:132-140
Available online: 2015-03-10
The aim of this study was to evaluate the long-term usefulness of intraportal injection of the bone marrow-derived mesenchymal stem cells (BM-MSCs) in limitation of experimentally induced ischemia-reperfusion injury (IRI) in a rat model.
Material and Methods: Twenty Wistar rats were divided into 3 groups: donor group (n=5), study group (n=10), and control group (n=5). IRI was performed using a modified hanging-weight system after left portal triad occlusion in study group animals. Isolated autologous BM-MSCs were labeled with fluorochrome PKH-26 then intraportally injected into the rats in the study group. Control group animals were intraportally injected with 1 ml of PBS. Follow-up was 3 months, after which animals were sacrificed for histopathological examination. Migration of BM-MSCs into different organs was examined.
Results: H&E staining of liver tissue sections from “time zero” biopsies did not show many irregularities in structural or histological construction compared to liver sections from the control group. However, a small amount of centrilobular hepatocyte necrosis and coagulative necrosis with neutrophil infiltration areas was observed in liver sections of the study group. The migration assay of BM-MSCs labeled with PKH-26 showed the highest positive BM-MSCs staining (6%) in the spleen, while few positively stained cells were found (2%) in liver sections. No BM-MSCs were detected in brain, kidney, or lung tissues.
Conclusions: These results suggest that intraportal bone marrow-derived mesenchymal stem cell injection is safe and cells do not migrate chaotically to other organs after targeted implementation.
Keywords: mesenchymal stromal cells, Reperfusion Injury, Tissue Engineering