Антипролиферативное и проапоптотическое действие — терапевтическая активность провоспалительных макрофагов при эндометриозе

Therapeutic activity of proinflammatory macrophages in endometriosis is driven by their antiproliferative and proapoptotic action

Relevance. Despite longstanding recognition of endometriosis, there’s an absence of effective treatment. Existing treatments carry significant risk, so research into cell therapy is gaining popularity. Macrophages are a promising agent. A previous study using an animal model demonstrated that introducing proinflammatory macrophages led to a significant reduction in endometriosis lesions. The aim of the study is to analyze the effect of macrophages with a proinflammatory phenotype introduced into an animal model on the proliferation and survival of cells in endometriosis lesions. Materials and Methods. A syngeneic model of endometriosis was obtained in female C57Bl/6 mice by intraperitoneal transplantation of uterine fragments from a donor mouse. RAW264.7 mouse macrophages were utilized as the cellular agent. The animals were then divided into groups: “Control” comprised mice that did not receive macrophage therapy; “Control of therapy” comprised mice that received unpolarized RAW264.7 macrophages; and “Therapy” comprised mice with endometriosis that were injected with RAW264.7 macrophages with a proinflammatory phenotype. Results and Discussion. Consequently, the administration of macrophages with a proinflammatory phenotype resulted in a significant decrease in the production of the proliferation marker protein Ki-67 and a significant increase in the production of effector caspase 3 in the cells of endometriosis lesions compared to the “Control” group. Concurrently, the level of production of the tumor suppressor protein p53, which is involved in the initiation of apoptosis in cells, was comparable to that in the “Control” group. This is in contrast to the group of animals that received unpolarized macrophages. Conclusion. We found that the anti-endometriosis activity of macrophages with a proinflammatory phenotype is associated with the fact that their introduction suppressed the proliferation of endometriosis cells and enhanced their apoptotic death through the activation of p53 and caspase 3. © Artemova D.A., Elchaninov A.V., Vishnyakova P.A., 2025.