Massive loss of neurons following brain injury or disease is the primary cause of central nervous system dysfunction. Recently, much research has been conducted on how to compensate for neuronal loss in damaged parts of the nervous system and thus restore functional connectivity among neurons. Direct somatic cell differentiation into neurons using pro-neural transcription factors, small molecules, or microRNAs, individually or in association, is the most promising form of neural cell replacement therapy available. This method provides a potential remedy for cell loss in a variety of neurodegenerative illnesses, and the development of reprogramming technology has made this method feasible. This article provides a comprehensive review of reprogramming, including the selection and methods of reprogramming starting cell populations as well as the signaling methods involved in this process. Additionally, we thoroughly examine how reprogramming astrocytes into neurons can be applied to treat stroke and other neurodegenerative diseases. Finally, we discuss the challenges of neuronal reprogramming and offer insights about the field.
3 June 2020 in The Journal of Clinical Endocrinology & Metabolism
Background Myeloid-derived suppressor cells (MDSCs) have become increasingly recognized as facilitators of tumor development. However, the role of MDSCs in papillary thyroid carcinoma (PTC) progression has not been clearly explored. Objective: We aimed to evaluate the levels as well as function of circulating MDSCs in PTC. Methods The proportion of circulating PMN-MDSCs and M-MDSCs from patients with PTC or benign thyroid nodules and healthy controls was measured using flow cytometry. For immunosuppressive activity analysis, sorted circulating MDSCs were co-cultured with CD3/CD28-costimulated T lymphocytes and the proliferation of T cells was determined. PTC cell lines (TPC-1 and BC-PAP) were co-cultured with PMN-MDSCs, and the effects on cell migration, invasion, proliferation and apoptosis were evaluated. The differential expressed miRNAs and mRNAs and their function were also explored in TPC-1 cells cocultured with or without PMN-MDSCs. Results PMN-MDSCs were increased in the peripheral blood mononuclear cells (PBMC) of patients with PTC. Circulating PMN-MDSCs displayed strong T cell suppressive activity. PTC cells demonstrated enhanced invasive capabilities in vitro and in vivo when co-cultured with sorted PMN-MDSCs. PMN-MDSCs decreased expression of miR-486-3p and activated NF-κB2, a direct target of miR-486-3p. Rescue of miR-486-3p diminished the cell migration and invasion induced by PMN-MDSCs. Conclusion Collectively, our work indicates that circulating PMN-MDSCs promote PTC progression. By suppressing miR-486-3p, PMN-MDSCs promote the activity of the NF-κB2 signaling pathway, resulting in accelerated invasion of PTC cells, which may provide new therapeutic strategies for treatment of thyroid cancer.
1 November 2014 in Journal of Evidence-Based Medicine
Nervous system diseases present significant challenges to the neuroscience community due to ethical and practical constraints that limit access to appropriate research materials. Somatic cell reprogramming has been proposed as a novel way to obtain neurons. Various emerging techniques have been used to reprogram mature and differentiated cells into neurons. This review provides an overview of somatic cell reprogramming for neurological research and therapy, focusing on neural reprogramming and generating different neural cell types. We examine the mechanisms involved in reprogramming and the challenges that arise. We herein summarize cell reprogramming strategies to generate neurons, including transcription factors, small molecules, and microRNAs, with a focus on different types of cells.. While reprogramming somatic cells into neurons holds the potential for understanding neurological diseases and developing therapeutic applications, its limitations and risks must be carefully considered. Here, we highlight the potential benefits of somatic cell reprogramming for neurological disease research and therapy. This review contributes to the field by providing a comprehensive overview of the various techniques used to generate neurons by cellular reprogramming and discussing their potential applications.