A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of autologous human induced pluripotent stem(-like) cells

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from autologous human iPS cells or iPS cell-like cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-4, “Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Autologous Human Induced Pluripotent Stem(-Like) Cells, ” issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper addresses various aspects of products derived from autologous human iPS cells (or iPS cell-like cells), in addition to similar points to consider that are described previously for autologous human stem cell-based products. Major additional points include (1) possible existence of autologous human iPS cell-like cells that are different from iPS cells in terms of specific biological features; (2) the use of autologous human iPS(-like) cells as appropriate starting materials for regenerative medicine, where necessary and significant; (3) establishment of autologous human iPS(-like) cell lines and their characterization; (4) cell banking and/or possible establishment of intermediate cell lines derived from autologous human iPS(-like) cells at appropriate stage(s) of a manufacturing process, if necessary; and (5) concerns about the presence of undifferentiated cells in the final product; such cells may cause ectopic tissue formation and/or tumorigenesis. The ultimate goal of this guidance is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities

Development of an autonomous surface vehicle for monitoring underwater vehicles

JAMSTEC has developed and operated several AUVs (Autonomous Underwater Vehicle) as platform for scientific investigation and explorations of seabed mineral resources. Conventionally, a support vessel monitors only one AUV during its whole dive for safety and positioning. We propose an operation of multiple AUVs using an ASV (Autonomous Surface Vehicle) to improve survey efficiency. For this purpose, JAMSTEC has been developing an ASV “MAINAMI” with a length of 6 meters since 2013. It has a diesel engine, two thrusters and a rudder. The vehicle is equipped with an acoustic communication device and a satellite one, in order to relay information between an AUV and operators on a ship or on land.Date of Conference: 19-22 October 2015http://www.godac.jamstec.go.jp/darwin/cruise/kaiyo/ky15-e01/

Dives of cruising-AUV "JINBEI" to methane hydrate area on Joetsu knoll and Umitaka Spur

Autonomous Underwater Vehicle "JINBEI", constructed in 2012, is a cruising type AUV with a weight of 2 ton and a length of 4.0m. The major purposes are observation of underwater CO2 distribution in deep sea and exploration of seabed mineral resources. It has four rear-thrusters, two mid-ship azimuthal thrusters, and a rear X-rudder. The AUV is equipped with three main sensors; a multi-beam echo sounder, a side scan sonar, and a hybrid CO2-pH sensor. During KY12-10 cruise in August 2012, we deployed "JINBEI" at a methane hydrate area in Joetsu knoll and Umitaka Spur, Japan Sea. The depth of the area is 850-950m. The vehicle cruised over the methane hydrate area at a speed of 2 knots. We obtained high-resolution side scan images of hydrate mounts as well as methane plumes. At same time, the CO2-pH sensor detected the methane plumes indirectly. Through the dives, we confirmed that the cruising AUV "JINBEI" is one of powerful tool for survey of scientific observations.Date of Conference: 23-27 September 2013http://www.godac.jamstec.go.jp/darwin/cruise/kaiyo/ky12-10/

資源探査AUVのデザインコンセプトと開発状況

第29回日本ロボット学会学術講演会（2011年9月7日～9日, 芝浦工業大学豊洲キャンパス

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

SARS-CoV-2オミクロンBA.2.75株（通称ケンタウロス）のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5

ASV MAINAMI for AUV monitoring and its sea trial

JAMSTEC has proposed an operation of multiple AUVs using an ASV (Autonomous Surface Vehicle) to improve survey efficiency. For this purpose, an ASV “MAINAMI” with a length of 6 meters has been developed since 2013. The vehicle is equipped with an acoustic communication device and a satellite one, in order to relay information between an AUV and operators on a ship or on land. In February 2016, its sea trials were carried out at Suruga-Bay. The performance of its solo navigation was verified through the sea trial. And, the ASV succeeded in tracking of a deep-tow as a simulated curing-type AUV

β-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisions

Asymmetric division is an important property of stem cells. In Caenorhabditis elegans, the Wnt/β-catenin asymmetry pathway determines the polarity of most asymmetric divisions. The Wnt signalling components such as β-catenin localize asymmetrically to the cortex of mother cells to produce two distinct daughter cells. However, the molecular mechanism to polarize them remains to be elucidated. Here, we demonstrate that intracellular phospholipase A1 (PLA1), a poorly characterized lipid-metabolizing enzyme, controls the subcellular localizations of β-catenin in the terminal asymmetric divisions of epithelial stem cells (seam cells). In mutants of ipla-1, a single C. elegans PLA1 gene, cortical β-catenin is delocalized and the asymmetry of cell-fate specification is disrupted in the asymmetric divisions. ipla-1 mutant phenotypes are rescued by expression of ipla-1 in seam cells in a catalytic activity-dependent manner. Furthermore, our genetic screen utilizing ipla-1 mutants reveals that reduction of endosome-to-Golgi retrograde transport in seam cells restores normal subcellular localization of β-catenin to ipla-1 mutants. We propose that membrane trafficking regulated by ipla-1 provides a mechanism to control the cortical asymmetry of β-catenin

Working-AUV "Otohime" and its sea trials at Sagami Bay

Since October 2010, JAMSTEC has developed two autonomous uderwater vehicles (AUVs); a cruising-AUV "Jinbei" and a working-AUV "Otohime". Their major purposes are to observe underwater CO2 distribution around carbon dioxide capture and storage field, and to explore seabed mineral resources in Japan's EEZ. The cruising-AUV performs wide area survey with sonars and chemical sensors. According to the survey results, the working-AUV "Otohime" accesses feature points and observes seafloor in detail, with its chemical sensors, cameras, and a manipulator. In this paper, we introduce the newly developed AUV "Otohime" and its sea trials at Sagami Bay. Through two dives at the depth of 80-120m for total 3 hours operation, we verified the performance of the overall hardware / software systems.IEEE International Symposium on Underwater Technology (UT2013, 5-8 March 2013, University of Tokyo, Japan)http://www.godac.jamstec.go.jp/darwin/cruise/kaiyo/ky12-05/