After transplantation of cells, tissues, or organs, it is important to control inflammation to prevent graft rejection. This can be difficult as continuous injuries due to chronic rejection can pose serious problems. A new study has reported that neutralizing the cell signaling molecule- tumor necrosis factor (TNF), can prevent cascades of injurious molecules and signals after cell transplantation.
The study conducted by researchers from Albert Einstein College of Medicine is published in the journal The American Journal of Pathology
Director of the research team Sanjeev Gupta, MD, Department of Medicine and of Pathology, and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA said, "New insights into immune inflammatory mediators indicate that rejection and tissue injury can be avoided with available drugs. The ability to prevent and/or control tissue injury will improve graft survival for transplantation medicine, advance use of cells and tissues for regenerative medicine, and offer insights for controlling inflammation-related tissue injury in other circumstances."
To study the factors that work in tissue rejection, the researchers have developed liver cell transplantation models in laboratory rats with or without immunosuppression, by using drugs routinely given to humans. Inflammation was studied by using gene expression to determine the activation of soluble signals associated with various cell types.
The study found differences in the expression of 40-50 soluble networks particularly in the activation of TNF, a major inflammatory mediator, and its cellular receptors is prominent, persisting over the long term.
By blocking TNF, the activation of most other inflammatory signals was stopped, revealing that it is important, activating the cytokines, chemokines, and receptors arising from the body's immune systems defending against foreign material like microbes, viruses, and mismatched transplants.
The role of TNF was further established by neutralizing it with drugs like etanercept or thalidomide to improve cell transplant outcomes alongside conventional immunosuppression with tacrolimus and mycophenolate mofetil.
The gene expression showed that by blocking TNF decreases the recruitment and activity of inflammatory cells. Other studies show that blocking TNF led to superior survival and proliferation of transplanted cells, regenerating the liver far more effectively.
Dr. Gupta said, "The translational potential of these findings is exciting because the additional inflammatory markers and genes offer further means for diagnosing the pathology of organ rejection in individuals. This type of inflammatory interference will decrease tissue injury, promote graft survival, and survival of transplanted cells and engineered tissues, and help advance organ regeneration. The inflammatory cascades orchestrated through TNF also hold lessons for the pathology in other less well understood conditions, such as COVID-19."