OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease.

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5+ (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4+ iOPCs was similar to that of O4+ OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes. Notably, engrafted iOPCs remyelinated the brains of adult shiverer mice and experimental autoimmune encephalomyelitis mice with MOG-induced 14 weeks after transplantation. In conclusion, our study may contribute to the development of therapeutic approaches for neurological disorders, as well as facilitate the understanding of the molecular mechanisms underlying glial development.

Tissue inhibitor of metalloproteinase proteins inhibit teratoma growth in mice transplanted with pluripotent stem cells.

Pluripotent stem cells (PSCs) can serve as an unlimited cell source for transplantation therapies for treating various devastating diseases, such as cardiovascular diseases, diabetes, and Parkinson's disease. However, PSC transplantation has some associated risks, including teratoma formation from the remaining undifferentiated PSCs. Thus, for successful clinical application, it is essential to ablate the proliferative PSCs before or after transplantation. In this study, neural stem cell-derived conditioned medium (NSC-CM) inhibited the proliferation of PSCs and PSC-derived neural precursor (NP) cells without influencing the potential of PSC-NP cells to differentiate into neurons in vitro and prevented teratoma growth in vivo. Moreover, we found that the NSC-CM remarkably decreased the expression levels of Oct4 and cyclin D1 that Oct4 directly binds to and increased the cleaved-caspase 3-positive cell death through the DNA damage response in PSCs and PSC-NPs. Interestingly, we found that NSCs distinctly secreted the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 proteins. These proteins suppressed not only the proliferation of PSCs in cell culture but also teratoma growth in mice transplanted with PSCs through inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 activity. Taken together, these results suggest that the TIMP proteins may improve the efficacy and safety of the PSC-based transplantation therapy.

Association between Smoking and Periodontal Disease in Korean Adults: The Fifth Korea National Health and Nutrition Examination Survey (2010 and 2012).

BACKGROUND: This study aimed to evaluate an association between smoking, smoking cessation, and periodontal disease in Korean adults. METHODS: The data were collected from 8,336 participants, aged between 20 and 64 years, who participated in the fifth Korea National Health and Nutrition Examination (2010 and 2012). Smoking status was assessed using self-administered questionnaires. Periodontal disease was defined as a community periodontal index ≥3 points. Logistic regression analysis was used to evaluate an association between smoking, smoking cessation, and periodontal disease after adjusting for age, sex, education, monthly income, diabetes, obesity, alcohol intake, and frequency of tooth brushing. RESULTS: The risk of periodontal disease was higher among current smokers (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.21-1.83) than never smokers. Among current smokers, the risk of periodontal disease was increased in smokers of ≥10 cigarettes/d, ≥20 years duration, and >10 pack-years compared with never smokers (P<0.05). Among former smokers, the risk of periodontal disease after 10 years since cessation declined to 0.56 (95% CI, 0.42-0.75) compared with current smokers and was indistinguishable statistically from never smokers. CONCLUSION: Periodontal disease is significantly associated with smoking status in Korean adults.