Adult Human Multipotent Neural Cells Could Be Distinguished from Other Cell Types by Proangiogenic Paracrine Effects via MCP-1 and GRO.

Adult human multipotent neural cells (ahMNCs) are unique cells derived from adult human temporal lobes. They show multipotent differentiation potentials into neurons and astrocytes. In addition, they possess proangiogenic capacities. The objective of this study was to characterize ahMNCs in terms of expression of cell type-specific markers, in vitro differentiation potentials, and paracrine factors compared with several other cell types including fetal neural stem cells (fNSCs) to provide detailed molecular and functional features of ahMNCs. Interestingly, the expression of cell type-specific markers of ahMNCs could not be differentiated from those of pericytes, mesenchymal stem cells (MSCs), or fNSCs. In contrast, differentiation potentials of ahMNCs and fNSCs into neural cells were higher than those of other cell types. Compared with MSCs, ahMNCs showed lower differentiation capacities into osteogenic and adipogenic cells. Moreover, ahMNCs uniquely expressed higher levels of MCP-1 and GRO family paracrine factors than fNSCs and MSCs. These high levels of MCP-1 and GRO family mediated in vivo proangiogenic effects of ahMNCs. These results indicate that ahMNCs have their own distinct characteristics that could distinguish ahMNCs from other cell types. Characteristics of ahMNCs could be utilized further in the preclinical and clinical development of ahMNCs for regenerative medicine. They could also be used as experimental references for other cell types including fNSCs.

Influence of Facial Flushing on Pre- or Type 2 Diabetes Risk according to Alcohol Consumption in Korean Male.

BACKGROUND: This study aims to examine the association between alcohol consumption and the risk of pre- or type 2 diabetes mellitus (T2DM) by alcohol-induced flushing response in Korean male adults, particularly based on their body mass index (BMI). METHODS: This study selected 1,030 (158 non-drinkers, 364 flushers, and 508 non-flushers) male adults who had medical checkups. A logistic regression analysis was used to compare the association between alcohol consumption and the risk of pre- or T2DM. RESULTS: In both the normal-weight group (BMI <23 kg/m2) and the overweight group (BMI ≥23 kg/m2 and <25 kg/ m2), the flushers had a higher risk of pre- or T2DM (odds ratio, 95% confidence interval) when consuming more than 8 drinks of alcohol per week than the non-drinkers (normal-weight group: 3.43, 1.06-11.07; overweight group: 4.94, 1.56-15.67). But in the non-flushers among the normal-weight group and the overweight group, there was no significant difference compared to non-drinkers regarding the risk of pre- or T2DM. Obese flushers had a significantly higher risk of pre- or T2DM when consuming more than 4 drinks of alcohol per week than the non-drinkers (>4 and ≤8 drinks: 2.64, 1.10-6.36; >8 drinks: 2.42, 1.11-5.27). However, obese non-flushers had only a significant higher risk of pre- or T2DM when consuming more than 8 drinks of alcohol per week than the non-drinkers (2.72, 1.39-5.30). CONCLUSION: These results suggest that obese flushers have an increased risk of developing pre- or T2DM even with less alcohol consumption.

Relationship between Alcohol Consumption and Ocular Pressure according to Facial Flushing in Korean Men with Obesity.

BACKGROUND: This study aimed to examine the relationship between alcohol consumption and intraocular pressure (IOP) according to facial flushing in Korean men with obesity. METHODS: The study included 479 Korean men with a body mass index of ≥25 kg/m2 (75 non-drinkers, 174 with drinking-related facial flushing, and 230 without facial flushing) who underwent health check-ups between October 1, 2016 and March 31, 2017. Multivariate logistic regression was used to assess the relationship between alcohol consumption and high IOP (≥21 mm Hg). RESULTS: Flushers consuming ≤16 drinks per week had a significantly higher risk of high IOP than non-drinkers, depending on alcohol consumption (≤8 standard drinks: odds ratio [OR], 4.49; 95% confidence interval [CI], 1.05- 19.25; >8 but ≤16 standard drinks: OR, 8.14; 95% CI, 1.37-48.45). However, when the consumption was >16 drinks per week, the high IOP risk did not significantly increase (OR, 0.71; 95% CI, 0.05-10.69). In addition, there was no significant relationship between alcohol consumption and high IOP among non-flushers consuming ≤8 drinks per week (OR, 2.07; 95% CI, 0.52-8.19). However, a significantly increased risk of high IOP was observed among nonflushers consuming >8 drinks per week, depending on alcohol consumption (>8 but ≤16 standard drinks: OR, 4.84; 95% CI, 1.14-20.61; >16 standard drinks: OR, 4.08; 95% CI, 1.02-16.26). CONCLUSION: This study suggests that obese men with alcohol flush reactions may have an increased risk of high IOP with the consumption of smaller amounts of alcohol than non-flushers.

Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion.

The RUNX1-RUNX1T1 fusion is a frequent chromosomal alteration in acute myeloid leukemias (AMLs). Although RUNX1-RUNX1T1 fusion protein has pivotal roles in the development of AMLs with the fusion, RUNX1-RUNX1T1, fusion protein is difficult to target, as it lacks kinase activities. Here, we used bioinformatic tools to elucidate targetable signaling pathways in AMLs with RUNX1-RUNX1T1 fusion. After analysis of 93 AML cases from The Cancer Genome Atlas (TCGA) database, we found expression of 293 genes that correlated to the expression of the RUNX1-RUNX1T1 fusion gene. Based on these 293 genes, the cyclooxygenase (COX), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) pathways were predicted to be specifically activated in AMLs with RUNX1-RUNX1T1 fusion. Moreover, the in vitro proliferation of AML cells with RUNX1-RUNX1T1 fusion decreased significantly more than that of AML cells without the fusion, when the pathways were inhibited pharmacologically. The results indicate that novel targetable signaling pathways could be identified by the analysis of the gene expression features of AMLs with non-targetable genetic alterations. The elucidation of specific molecular targets for AMLs that have a specific genetic alteration would promote personalized treatment of AMLs and improve clinical outcomes.

Angiogenic Capacity of Dental Pulp Stem Cell Regulated by SDF-1α-CXCR4 Axis.

Previously, the perivascular characteristics of dental pulp stem cells (DPSCs) were reported, which suggested the potential application of DPSCs as perivascular cell source. In this study, we investigated whether DPSCs had angiogenic capacity by coinjection with human umbilical vein endothelial cells (HUVECs) in vivo; in addition, we determined the role of stromal cell-derived factor 1-α (SDF-1α) and C-X-C chemokine receptor type 4 (CXCR4) axis in the mutual interaction between DPSCs and HUVECs. Primarily isolated DPSCs showed mesenchymal stem cell- (MSC-) like characteristics. Moreover, DPSCs expressed perivascular markers such as NG2, α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor ß (PDGFRß), and CD146. In vivo angiogenic capacity of DPSCs was demonstrated by in vivo Matrigel plug assay. We could observe microvessel-like structures in the coinjection of DPSCs and HUVECs at 7 days postinjection. To block SDF-1α and CXCR4 axis between DPSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into Matrigel plug. No significant microvessel-like structures were observed at 7 days postinjection. In conclusion, DPSCs have perivascular characteristics that contribute to in vivo angiogenesis. The findings of this study have potential applications in neovascularization of engineered tissues and vascular diseases.

The Significance of SDF-1α-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells.

Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, αsmooth muscle actin, platelet-derived growth factor receptor ß, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HU-VECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the SDF-1α and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the peri-vascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.