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Injection of rat mesenchymal stem cells leads to their homing and differentiation in the liver in a blunt liver trauma model
Background: The liver heals remarkably after different forms of injury. However healing can be lengthy following high-grade injuries. We hypothesize that injected mesenchymal stem cells (MSCs) could locate in the liver and differentiate into hepatocytes after blunt trauma using a rat liver trauma model.
Methods: Blunt liver trauma was induced in Lewis rats. MSCs were transfected with LacZ retrovirus so that they express the beta-galactosidase enzyme giving their nuclei a blue color on light microscopy. Each rat received a dose of MSCs (n = 6 × 106) within 24 h of trauma. Through different steps of the experiment the route of injection was the tail vein (TV) in nine rats the portal vein (PV) in 19 rats and directly to the injured liver (DI) in four rats. Rats were euthanized at 48 h or 7 days after the injection of MSCs. Livers were harvested and examined under light microscopy to identify the MSCs.
Results: Liver sections showed localization and migration of MSCs to trauma sites in the PV group euthanized at 48 h (3/10 rats). Some MSCs differentiated into hepatocytes. 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.
Discussion: MSCs can locate and differentiate into liver-like cells in blunt liver injury. Portal vein injection of MSC has emerged as the most effective method of delivery to the liver among the other methods. Optimizing homing to injured tissue and evaluating differentiated stem cell functionality are future areas of research.