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Objectives: Gene therapy using viral vectors and antibody-based therapies continue to expand within the pharmaceutical market. We evaluated whether Cellhesion ® VP, a chitin-based material, can be used as 3D culture platform for cell lines used for the production of antibodies and viral vectors., Results: The results of Cell Counting Kit-8 assay and LDH assay revealed that Cellhesion ® VP had no adverse effect to Human Embryonic Kidney (HEK) 293, A549 and Chinese hamster ovary (CHO) DG44-Interferon-β (IFN) cells. Cell growth analyses showed that Cellhesion ® VP supported the 3D culture of HEK293, A549 and CHO DG44- IFN-β cells with a spherical morphology. Importantly, subculture of these cell lines on Cellhesion ® VP was easily performed without trypsinization because cells readily transferred to newly added scaffold. Our data also suggest that CHO DG44-IFNβ, cultured on Cellhesion ® VP secreted IFNβ stably and continuously during the culture period., Conclusions: Cellhesion ® VP provides a simple and streamlined expansion culture system for the production of biopharmaceuticals., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Mesenchymal stem cell (MSC) transplantation, in particular allogeneic transplantation, is a promising therapy for a variety of diseases. However, before performing allograft treatment it is necessary to find suitable donors, establish culture methods that maintain cell quality, and reduce cell production costs. Here, we present a new method of producing allogeneic MSCs combining human umbilical cord-derived mesenchymal stem cells (UCMSCs) and chitin-based polysaccharide fibers (Cellhesion ® MS). UCMSC numbers significantly increased, and cells grew as dispersed spheres on Cellhesion ® MS. Subsequent biological analyses showed that the expression levels of stemness-related and migration-related genes were significantly upregulated, including octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), and C-X-C chemokine receptor type 4 (CXCR4). The secretion levels of paracrine factors such as prostaglandin E2 (PGE 2 ), TNFα-stimulating gene (TSG)-6, fibroblast growth factor 2 (bFGF), and Angiogenin (Ang) from UCMSCs using Cellhesion ® MS were significantly higher than with microcarrier and U-bottom plate culture. In addition, culture supernatant from UCMSCs with Cellhesion ® MS had better angiogenic potential than that from monolayer cultured UCMSCs. Furthermore, we succeeded in a scaled-up culture of UCMSCs with Cellhesion ® MS using a closed culture bag. Therefore, Cellhesion ® MS is a key material for producing high-quality UCMSCs in a three-dimensional (3D) culture system.

Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer cells through up-regulation of EGF receptor (EGFR) signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2-knockdown DU145 cells. Mechanistically, we found that STAP-2 interacted with EGFR and enhanced its stability by inhibiting c-CBL-mediated EGFR ubiquitination. Our results indicate that STAP-2 promotes prostate cancer progression via facilitating EGFR activation., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Chronic myeloid leukemia is a clonal disease characterized by the presence of the Philadelphia chromosome and its oncogenic product, BCR-ABL, which activates multiple pathways involved in cell survival, growth promotion, and disease progression. We previously reported that in murine hematopoietic Ba/F3 cells, signal transducing adaptor protein-2 (STAP-2) binds to BCR-ABL and up-regulates BCR-ABL phosphorylation, leading to enhanced activation of its downstream signaling molecules. The binding of STAP-2 to BCR-ABL also influenced the expression levels of chemokine receptors, such as CXCR4 and CCR7. For the induction of CCR7 expression, signals mediated by the MAPK/ERK pathway were critical in Ba/F3 cells expressing BCR-ABL and STAP-2. In addition, STAP-2 cooperated with BCR-ABL to induce the production of CCR7 ligands, CCL19 and CCL21. Our results demonstrate a contribution of CCR7 to STAP-2-dependent enhancement of BCR-ABL-mediated cell growth in Ba/F3 cells., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The promyelocytic leukemia protein PML acts as a tumor suppressor by forming transcription-regulatory complexes with a variety of repressor proteins. In the present study, we found that endogenous PML suppresses interleukin (IL)-6-induced gene expression as well as phosphorylation and transcriptional activation of STAT3 in hepatoma cells. We also found that PML-mediated suppression of IL-6-induced STAT3 activation by disrupting interactions between STAT3 and HDAC3. These results indicate that PML modulates IL-6-induced STAT3 activation and hepatoma cell growth by interacting with HDAC3., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ectoparasitic arthropods are often vectors of rickettsiosis. We conducted a survey of ectoparasites on U.S. military facilities throughout Japan with the use of specimens submitted by pest control, public health, and veterinary personnel. Over 1,600 individual ectoparasites were collected. Fifteen species were identified, including several significant vectors of human diseases such as scrub typhus and rickettsial spotted fevers. These ectoparasites included Ctenocephalides felis , Haemaphysalis longicornis, Ixodes persulcatus , Leptotrombidium fuji, Leptotrombidium pallidum, and Rhipicephalus sanguineus . Rickettsial agents were detected by PCR and DNA sequencing. These included Bartonella henselae , Bartonella japonica, a novel Bartonella, Coxiella burnetii , an unnamed Coxiella, Ehrlichia canis , Orientia tsutsugamushi , Rickettsia typhi , and "Rickettsia Rf2125"/"Rickettsia cf1and5".