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Elimination of allogeneic multipotent stromal cells by host macrophages in different models of regeneration
Authors:Irina Arutyunyan  Andrey Elchaninov  Timur Fatkhudinov  Andrey Makarov  Evgeniya Kananykhina  Natalia Usman  Galina Bolshakova  Valeria Glinkina  Dmitry Goldshtein  Gennady Sukhikh
Abstract:Allogeneic multipotent stromal cells were previously thought to be poorly recognized by host immune system; the prolonged survival in host environments was explained by their immune privileged status. As long as the concept is currently reconsidered, the routes of elimination of allogeneic multipotent stromal cells by host immunity must be taken into account. This is necessary for correct comprehension of their therapeutic action. The study was focused upon survival of umbilical cord-derived allogeneic multipotent stromal cells in different rat models of tissue regeneration induced by partial hepatectomy or by critical limb ischemia. The observations were carried out by means of vital labeling of the cells with PKH26 prior to injection, in combination with differential immunostaining of host macrophages with anti-CD68 antibody. According to the results, allogeneic multipotent stromal cells are specifically eliminated by host immune system; the efficacy can reach 100%. Massive clearance of transplanted cells by host macrophages is accompanied by appropriation of the label by the latter, and this is a pronounced case of misleading presentation of exogenous label by host cells. The study emphasizes the role of macrophages in host response and also the need of additional criteria for correct data interpretation.
Keywords:Allogeneic transplantation   CD68 antigen   macrophages   multipotent stromal cells   mesenchymal stromal cells
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