title: Long-term influence of bone marrow-derived mesenchymal stem cells on liver ischemia-reperfusion injury in a rat model.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Nowacki
authors.affiliation: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Nazarewski
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Pokrywczyńska
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kloskowski
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Tyloch
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pietkun
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Jundziłł
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Rasmus
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Warda
authors.affiliation: Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Gagat
authors.affiliation: Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Grzanka
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bodnar
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszałek
authors.affiliation: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Samy L
authors.initials: SL
authors.lastname: Habib
authors.affiliation: Chair of Regenerative Medicine, Department of Tissue Engineering, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Drewa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome