INJECTION OF RAT MESENCHYMAL STEM CELLS LEADS TO HOMING AND DIFFERENTIATION IN THE LIVER IN A BLUNT LIVER TRAUMA MODEL

Abstract

Background: The liver heals remarkably after different forms of injuries. However, healing time can be lengthy following high-grade blunt injuries. We hypothesize that injected bone marrow derived mesenchymal stem cells (MSC) could locate and differentiate to hepatocytes after blunt trauma using a rat liver trauma model. Methods: Blunt liver trauma was induced to Lewis rats. MSC were extracted from Lewis rats’ femurs and transfected with LacZ retrovirus so that they express B- galactosidase enzyme, giving their nuclei a blue color on light microscopy. Each rat received a single dose of BMDS (n=6 x 106) within 24 hours of trauma. Through different steps of the experiment, route of injection was the tail vein (TV) in 9 rats, the portal vein (PV) in 19 rats and directly to the injured liver (DI) in 6 rats. Rats were euthanized at 2, 7 days after injection of MSC. Livers were harvested and examined under light microscopy to identify the MSC. Results: Liver sections showed localization and active migration of MSC to trauma sites in the PV group euthanized at 48 hours (3/10 rats). Furthermore, some stem cells differentiated to hepatocytes. Although with fewer cells, similar findings were present in 1/9 rats euthanized at 7 days in the PV group. There was no evidence of MSC localization in TV and DI groups. 4 Conclusions: MSC can locate and differentiate to hepatocytes at blunt trauma site and may contribute to liver regeneration process. Portal vein injection of MSC has emerged as the most effective method of delivery to the liver following trauma among different delivery methods studied. This technique has the potential to become an effective therapeutic strategy to improve liver regeneration after severe blunt trauma. Methods of optimizing homing to injured tissue and evaluation of differentiated stem cell functionality are future areas of research.