Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing

Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-α, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL-6 and TNF-α, and an increased expression of IL-10. The GMSC-induced suppression of TNF-α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing. © AlphaMed Press

Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene

The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non-biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could maintain pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC.ope

Long-Term Survival in a Patient With Ruptured Hepatocellular Carcinoma

A 57-yr-old woman previously diagnosed with chronic hepatitis B was admitted via the emergency room because she suddenly developed epigastric pain with abdominal distension. On computed tomography (CT), a round enhancing mass was found on the left hepatic lobe with ascites in the peritoneal space. Bloody ascites were found upon tapping the ascites, and this led to the diagnosis of ruptured hepatocellular carcinoma (HCC). The patient was immediately treated with transcatheter arterial chemoembolization (TACE) including 50 mg of adriamycin and 10 mL of lipiodol, and then we performed left lateral segmentectomy 20 days later. To prevent recurrence of HCC by any micrometastasis, the patient subsequently received 8 cycles of adjuvant systemic chemotherapy (a regimen of epirubicin (50 mg/m2), cisplatin (60 mg/m2) and 5-fluorouracil (200 mg/m2)) at monthly intervals. After this, the patient has been regularly followed up and she shows no signs of tumor recurrence 7 years later. This case suggests that surgical resection and subsequent adjuvant systemic chemotherapy with using an ECF regimen may provide long-term survival for patients ruptured HCC

PCR Marker-Based Evaluation of the Eating Quality of Japonica Rice (Oryza sativa L.)

Evaluation of eating quality in early breeding generations of rice is critical to developing varieties with better palatability. This paper reports DNA markers associated with eating quality of temperate japonica rice and an evaluation method aided by multiple regression analysis. A total of 30 markers comprising STSs, SNPs, and SSRs were tested for their association with palatability using 22 temperate japonica varieties with different palatability values. Eating quality-related traits of the 22 varieties were also measured. Of the 30 markers, 18 were found to be significantly associated with palatability and, consequently, a model regression equation with an R2 value of 0.99 was formulated to estimate the palatability by the marker data set. Validation of the model equation using selected breeding lines indicated that the marker set and the equation are highly applicable to evaluation of the palatability of cooked rice in temperate japonica varieties

Tumor immune profiles noninvasively estimated by FDG PET with deep learning correlate with immunotherapy response in lung adenocarcinoma

Rationale: The clinical application of biomarkers reflecting tumor immune microenvironment is hurdled by the invasiveness of obtaining tissues despite its importance in immunotherapy. We developed a deep learning-based biomarker which noninvasively estimates a tumor immune profile with fluorodeoxyglucose positron emission tomography (FDG-PET) in lung adenocarcinoma (LUAD). Methods: A deep learning model to predict cytolytic activity score (CytAct) using semi-automatically segmented tumors on FDG-PET trained by a publicly available dataset paired with tissue RNA sequencing (n = 93). This model was validated in two independent cohorts of LUAD: SNUH (n = 43) and The Cancer Genome Atlas (TCGA) cohort (n = 16). The model was applied to the immune checkpoint blockade (ICB) cohort, which consists of patients with metastatic LUAD who underwent ICB treatment (n = 29). Results: The predicted CytAct showed a positive correlation with CytAct of RNA sequencing in validation cohorts (Spearman rho = 0.32, p = 0.04 in SNUH cohort; spearman rho = 0.47, p = 0.07 in TCGA cohort). In ICB cohort, the higher predicted CytAct of individual lesion was associated with more decrement in tumor size after ICB treatment (Spearman rho = -0.54, p < 0.001). Higher minimum predicted CytAct in each patient associated with significantly prolonged progression free survival and overall survival (Hazard ratio 0.25, p = 0.001 and 0.18, p = 0.004, respectively). In patients with multiple lesions, ICB responders had significantly lower variance of predicted CytActs (p = 0.005). Conclusion: The deep learning model that predicts CytAct using FDG-PET of LUAD was validated in independent cohorts. Our approach may be used to noninvasively assess an immune profile and predict outcomes of LUAD patients treated with ICB.