Up-Regulation of miR-1925 by Bone Marrow Mesenchymal Stem Cell (BMSC) Inhibits the Growth of Liver Cancer by Promoting the Anti-Tumor Activity of Natural Killer (NK) Cells

Hepatocellular carcinoma (HCC) seriously threatens human health and life quality. Natural killer (NK) cells play important roles in liver immune function. Bone marrow mesenchymal stem cell (BMSC) exosomes (Exo) participate in tissue damage. This study explored BMSC-Exo’s effect on NK cells’ anti-tumor activity. NK cells were isolated from the livers of mice with liver cancer. NK cells with or without BMSC-Exo treatment were co-cultured with liver cancer cells to assess cell proliferation. Administration of BMSC-Exo into mice with liver cancer significantly suppressed liver cancer cell growth. In addition, BMSC-Exo treatment significantly improved NK cells’ anti-tumor effect whic was related to BMSC-Exo-induced up-regulation of miR-1925. Implantation of BMSC-Exo into mice with liver cancer at different time periods can significantly suppress liver cancer cell growth. At the same time, BMSC-Exo implantation inhibited the expression of cell proliferation marker protein(Ki67). In vitro study found that BMSC-Exo treatment significantly increased miR-1925 level and the toxicity of NK cells to HCC cells. In addition, miR-1925 overexpression in NK cells significantly increased NK cells’ anti-tumor activity. In conclusion, this study proved that up-regulation of miR-1925 by BMSC can inhibit the growth of liver cancer by promoting the anti-tumor activity of NK cells.

Induced Pluripotent Stem Cell-Derived Neural Culture Model of Alzheimer’s Disease: A 3D Organoid Approach

Alzheimer’s disease (AD) is a progressive neurologic disorder that impacts a diverse population of older adults. As three-dimensional (3D) models are powerful tools for advancing AD studies, the authors have been developed AD cortical organoids to enable the observation of AD pathology at the cellular, tissue, and organ levels. For creating the model, APPSwe/Ind (APP) and PSEN1 (PS1) mutant genes were transfected into mouse induced pluripotent stem cells (iPSCs) following which the iPSC lines that expressed mutant APP and PS1 proteins were obtained. Then, using modified serum-free suspended embryoid body culture, AD cerebral organoids were made successfully at various ages. The AD model can show AD’s biochemical and pathological alterations, such as overexpressions of Aβ40 and Aβ42 and a decrease of GABAergic interneurons. The proposed model has the potential for implementation in many biomedical applications, including AD drug screening, stem cell transplant, and neuronal tissue engineering.