The research group New Therapies on Genes and Transplantation at the IDIBELL first studied the response of human NK cells (Natural Killer) against porcine chondrocytes (cartilage cells).
The results of the research, published in The Journal of Immunology, indicate that these cells, characteristic of the innate immune system play an important role in the rejection of xenotransplantation (from another species) of porcine chondrocytes.
NK cells are part, together with neutrophils and macrophages,of the first line of cellular defense and they are involved in not-acquired immune response, the innate response. They are responsible for identifying specific cell types (tumor, infection or foreign to the body) and they lyse them by toxicity.
The number of NK cells is a minority, but their importance is increasing in the field of transplantation, according to the study's lead author, Cristina Costa, "we see that innate immunity plays an important role in regulating of acquired immunity, which is critical for the rejection of transplanted organs".
The Costa team's goal is the porcine chondrocytes transplantation in humans to repair cartilage injuries. So they have studied "in vitro" response of human NK cells in the presence of pig cells. They noted that under conditions of transplant, high presence of antibodies and cytokines, human NK cells make a cytotoxic response and they lyse (destroy) foreign cells, in this case the chondrocytes.
"In this work we have characterized several molecules involved in the processes of adhesion and cytotoxicity of NK cells," explained the researcher, who believes that this work opens the way on how to continue the investigation "on the one hand we have to fight the deposition of antibodies that is a critical factor in increasing the toxicity and on the other we must work to reduce cell adhesion by modifying any of the molecules we have involved."
The next step for clinical application of xenotransplantation proposed by Costa cartilage would be "the genetic modification of porcine chondrocytes, so that human NK cells don't recognize them as foreign, thus avoiding rejection."
Transplantation of cartilage
Cartilage transplantation between humans is not been widely applied in the clinic but it has been successful in the regeneration of this tissue in traumatic injuries, especially in athletes. Autologous transplants are performed with cells from the same person and allogeneic ones with cells from another person, "in both cases," says Costa, "the limitation is the amount of cells. If we can get xenotransplantation it would increase the amount and quality of the cells available for transplantation of cartilage."
In the future, according to the researcher, "maybe we could apply the xenotransplantation of pig chondrocytes on osteoarthritis patients or even with rheumatoid arthritis" but warned Costa "in these cases are combined other inflammatory and immune processes hindering the outcome of the transplantation."
Researchers from the Institute of Immunology, University of Heidelberg in Germany have collaborated in the study.
Sommaggio R.*, Cohnen A, Watzl C. and Costa C.*. Multiple receptors trigger human NK cell-mediated citotoxicity against porcine chondrocytes. The Journal of Immunology.doi 10.4049/jimmunol.1100433