Regenerative Processing Plant, LLC, 34176 US Highway 19 N, Palm Harbor, FL 34684, USA.
Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
Int J Mol Sci. 2022 Apr 19;23(9):4487. doi: 10.3390/ijms23094487.
Therapeutic agents that are able to prevent or attenuate inflammation and ischemia-induced injury of neural and retinal cells could be used for the treatment of neural and retinal diseases. Exosomes derived from adipose tissue-sourced mesenchymal stem cells (AT-MSC-Exos) are extracellular vesicles that contain neurotrophins, immunoregulatory and angio-modulatory factors secreted by their parental cells. AT-MSC-Exos are enriched with bioactive molecules (microRNAs (miRNAs), enzymes, cytokines, chemokines, immunoregulatory, trophic, and growth factors), that alleviate inflammation and promote the survival of injured cells in neural and retinal tissues. Due to the nano-sized dimension and bilayer lipid envelope, AT-MSC-Exos easily bypass blood-brain and blood-retinal barriers and deliver their cargo directly into the target cells. Accordingly, a large number of experimental studies demonstrated the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases. By delivering neurotrophins, AT-MSC-Exos prevent apoptosis of injured neurons and retinal cells and promote neuritogenesis. AT-MSC-Exos alleviate inflammation in the injured brain, spinal cord, and retinas by delivering immunoregulatory factors in immune cells, suppressing their inflammatory properties. AT-MSC-Exos may act as biological mediators that deliver pro-angiogenic miRNAs in endothelial cells, enabling re-vascularization of ischemic neural and retinal tissues. Herewith, we summarized current knowledge about molecular mechanisms which were responsible for the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases, emphasizing their therapeutic potential in neurology and ophthalmology.
能够预防或减轻炎症和缺血引起的神经和视网膜细胞损伤的治疗剂可用于治疗神经和视网膜疾病。脂肪组织来源的间充质干细胞（AT-MSC-Exos）衍生的外泌体是含有神经营养因子、免疫调节和血管调节因子的细胞外囊泡，由其亲代细胞分泌。AT-MSC-Exos 富含生物活性分子（microRNAs (miRNAs)、酶、细胞因子、趋化因子、免疫调节、营养和生长因子），可减轻炎症并促进神经和视网膜组织中受损细胞的存活。由于纳米尺寸和双层脂质包膜，AT-MSC-Exos 很容易绕过血脑和血视网膜屏障，并将其货物直接递送到靶细胞。因此，大量的实验研究表明 AT-MSC-Exos 在治疗神经和视网膜疾病方面具有有益的作用。通过递送神经营养因子，AT-MSC-Exos 可防止受损神经元和视网膜细胞的凋亡，并促进神经突生成。AT-MSC-Exos 通过向免疫细胞中递送免疫调节因子来减轻受伤大脑、脊髓和视网膜中的炎症，抑制其炎症特性。AT-MSC-Exos 可作为生物介导物，在血管内皮细胞中递送促血管生成的 miRNAs，使缺血性神经和视网膜组织重新血管化。在此，我们总结了目前关于 AT-MSC-Exos 在治疗神经和视网膜疾病方面的有益作用的分子机制的知识，强调了它们在神经病学和眼科学中的治疗潜力。
