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The role of small extracellular vesicles in the regeneration of nervous tissue
Kristyna Sintakova, PhD student, Institute of Experimental Medicine of the CAS
Spinal cord injury (SCI) is a devastating condition with a complicated pathology and long-term functional impairment with no effective treatment [1]. Promising therapeutic approaches include the application of neural stem cells (NSCs), which have been shown to have neuroprotective and immunomodulatory effects in SCI [2]. The exact mechanism of their action has not yet been satisfactorily explained. Based on published works [3-5], it is suggested that the positive effect is mediated by small extracellular vesicles (sEVs) released by NSCs, mainly by miRNA contained in them.
A comprehensive characterization of sEVs derived from culture media of various cell types was performed, including detection of expressed exosomal markers and several neuroprotective miRNAs.
To evaluate therapeutic potential of sEVs, their suspension was applied on the injured nervous tissue in SCI in vitro model. This led to a decrease in the levels of proteins involved in pathophysiological and apoptotic processes compared to the injured tissue. When applied to an in vitro model, NSC-sEVs have shown stronger neuroprotective effect compared to mesenchymal stem cell derived sEVs.
Supported by GAUK 409222
Influence of Cervical Cancer-Derived Extracellular Vesicles on T-Lymphocyte Proliferation and Cytokine Secretion in PBMCs
Jordy Larco, PhD student , UMCG
Tumoral cells release more Extracellular vesicles (EVs) than normal cells and these may reach circulation and thereby distant tissues, resulting in systemic effects2. Cervical cancer is a burden on public health systems, mainly in developing countries. Persistent infection with high-oncogenic risk Human Papillomavirus (HPV) is the etiology factor for cervical cancer, as well as a significant percentage of other anogenital and oropharyngeal cancers. This family of small DNA viruses contains two bona fide oncogenes, E6 and E7. The oncoproteins E6 and E7 are pleiotropic proteins that promote p53 and pRB degradation, respectively. They also activate p65-NFKB, which transactivates the IL-6 gene, promoting IL-6 secretion and STAT3 chronic activation in HPV infected cells and leukocytes1.
We have shown that cervical cancer promotes systemic activation of STAT3. Preliminary data showed that EVs can induce phospho-STAT3 expression in PBMCs and modulate monocytes and T-lymphocytes activation. We hypothesized that cervical cancer EVs may be part of the cervical cancer triggered tolerogenic mechanisms, in part, via chronic STAT3 activation. Moreover, STAT3 is considered an oncogene in many types of cancer, promoting cell proliferation and survival and epithelial-mesenchymal transition. We have shown that monocytes internalize cervical cancer EVs and that these monocytes can inhibit T-cell activation.
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