Использование кишечных органоидов человека при воспалительных заболеваниях кишечника: от экспериментальной модели к регенеративной терапии

Abstract

Despite advances in the treatment of inflammatory bowel disease (IBD), current therapies have limited efficacy and can cause serious adverse reactions, which not only reduces the quality of life but also results in shorter life expectancy for patients. Therefore, it is necessary to develop new methods of diagnosis and find more effective ways of treatment. A significant breakthrough in the study of intestinal epithelial cells in various pathologies, including IBS, has been achieved by the establishment of three-dimensional (3D) organoid cultures that in vitro recreate intestinal epithelial tissue. Organoid cultures are derived from either somatic stem cells or pluripotent stem cells. These cells, grown under appropriate conditions, self-organize into specific spherical tissue structures with the properties and functions of gastrointestinal tissues. It has been shown that intestinal organoids may be a promising tool for assessing the molecular and functional impact on the intestinal epithelium of genetic and epigenetic changes associated with the gastrointestinal tract. To objectively evaluate the functional status of the intestinal epithelium in IBD, one needs to present organoid models together with the intestinal microbiota in order to determine the specific effect of bacteria on the epithelial barrier. Intestinal organoids are also being used to explore novel strategies for both direct drug exposure to the intestinal epithelium and targeted drug delivery, including nanoparticle and microparticle-based approaches, thereby reducing the limitations of systemic treatment. Finally, organoids serve as the basis of regenerative medicine for the treatment of IBD. New treatment techniques can be applied in patients with IBD in combination with immunoregulatory therapy and contribute to the achievement of prolonged clinical remission. Key words: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, organoid cultures, diagnosis, stem cells, regenerative medicine