👤 Hiroko Isoda

Cell-based therapy targeting spinal cord injury (SCI) is an attractive approach to promote functional recovery by replacing damaged tissue. We and other groups have reported the effectiveness of transplanting neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) in SCI animal models for neuronal replacement. Glial replacement is an additional approach for tissue repair; however, the lack of robust procedures to drive iPSCs into NS/PCs which can produce glial cells has hindered the development of glial cell transplantation for the restoration of neuronal functions after SCI. Here, we established a method to generate NS/PCs with gliogenic competence (gNS/PCs) optimized for clinical relevance and utilized them as a source of therapeutic NS/PCs for SCI. We could successfully generate gNS/PCs from clinically relevant hiPSCs, which efficiently produced astrocytes and oligodendrocytes in vitro. We also performed comparison between gNS/PCs and neurogenic NS/PCs based on single cell RNA-seq analysis and found that gNS/PCs were distinguished by expression of several transcription factors including HEY2 and NFIB. After gNS/PC transplantation, the graft did not exhibit tumor-like tissue formation, indicating the safety of them as a source of cell therapy. Importantly, the gNS/PCs triggered functional recovery in an SCI animal model, with remyelination of demyelinated axons and improved motor function. Given the inherent safety of gNS/PCs and favorable outcomes observed after their transplantation, cell-based medicine using the gNS/PCs-induction procedure described here together with clinically relevant iPSCs is realistic and would be beneficial for SCI patients. Show less

The medicinal plants can be used in the prevention or treatment of many diseases. Several studies concerning the potential of bioactive components in plants and food products and their link to obesity and related metabolic disorders, have been gaining big interest. Diabetes is a serious metabolic syndrome. Searching for alternative natural bioactive molecules is considered main strategy to manage diabetes through weight management. In the present study, an edible halophyte Nitraria retusa was selected and in vivo experiment was conducted using db/db model mice. We orally administrated its ethanol extract (NRE) to BKS.Cg-Dock7(m)+/+ Lepr(db/)J mice model for a period of 4 weeks. The effect was evaluated on the body weight and adiposity changes and on the biochemical parameters of db/db NRE-treated mice. The molecular mechanism underlying the anti-obesity effect was investigated by testing the gene expression related to hepatic lipid metabolism. NRE was found to significantly supress increases in body and fat mass weight, decreases triglycerides and LDL-cholesterol levels and enhances gene expression related to lipid homeostasis in liver showing anti-obesity actions. Our findings, indicate that NRE possesses potential anti-obesity effects in BKS.Cg-Dock7(m)+/+ Lepr(db/)J model mice and may relieve obesity-related symptoms including hyperlipidemia through modulating the lipolysis-lipogenesis balance. Show less