MiCell Technologies (United States)

Abstract There is an urgent need for effective solutions to replace liver functions in patients with acute liver failure (ALF). We describe here a human engineered liver tissue composed of induced pluripotent stem cell (iPSC)-derived liver organoids encapsulated within a non-degradable biomaterial. Unlike most stem cell–derived products, this encapsulated liver tissue (ELT) achieves functional maturation during manufacturing. When transiently implanted into the peritoneal cavity of immunocompetent mice with ALF, the human ELT improves survival, treats hepatic encephalopathy and promotes liver regeneration, without requiring immunosuppression. Based on robust processes and designed to overcome challenges such as foreign body reaction, loss of function and cryopreservation, the ELT does not require vascularization and provides immediate and long-lasting functional replacement. Once the liver regenerated, the ELT is explanted, leaving the subjects cured. Macroencapsulation prevents rejection by shielding the organoids from the host immune system, and minimizes the risk of tumorigenicity. The data shown demonstrate the ELT’s potential to be developed into a safe and effective off-the-shelf treatment that, if validated in upcoming clinical trials, could replace liver transplantation for many patients with ALF.

Bats represent natural reservoirs of several paramyxoviruses, raising concerns about the potential for these viruses to cause cross-species infections. In this study, we isolated two jeilongviruses belonging to the family Paramyxoviridae from oral swab samples of the Eastern bent-wing bat (Miniopterus fuliginosus) and Far Eastern myotis bat (Myotis bombinus) in Kagoshima Prefecture, Japan. Notably, this is the first report isolating bat paramyxoviruses in Japan. Genomic analyses revealed a high identity between Kagoshima isolates (PMV/Bat35 and PMV/Bat111) and jeilongvirus B16-40, previously isolated from a Schreiber's bent-wing bat (Miniopterus schreibersii) in South Korea in 2016. PMV/Bat35 infected and replicated in a range of cell lines derived from different animal species, although the level of syncytium formation varied among cell lines. Animal experiments revealed that Syrian hamsters inoculated intranasally with PMV/Bat35 did not exhibit clinical symptoms or significant weight loss. Nevertheless, viral genes were detected in the lungs and tracheas of Syrian hamsters on 2- and 5-day postinfection (dpi). Importantly, neutralizing antibodies against PMV/Bat35 developed in hamsters on 14 dpi. These results suggest that bat jeilongviruses can cross the species barriers. Our findings highlight the critical importance of ongoing monitoring and characterization of viruses circulating in bat populations to assess the risk of zoonotic outbreaks.

Organizations can more readily monitor and reposition their operations in fast-paced, competitive environments when their performance measurement systems provide them with relevant, timely, complete, and accurate information.i¾ i¾ Despite recognition of the need for such systems, much organizational performance measurement guidance consists primarily of descriptive approaches and anecdotes.i¾ i¾ There is a need for a structured approach to documenting and analyzing organization-wide performance measurement systems such as to address the organization, its environment, its measures, and its measurement infrastructure as an integrated whole.i¾ i¾ The purpose of this article is to describe a systems management approach and an associated process that have been developed to support the documentation and analysis of organization-wide performance measurement systems.i¾ i¾ A decision support system, The Organizational Performance Tracking & IMprovement Analysis System (OPTIMAS), was developed to automate use of the process and facilitate the documentation, analysis, evolution, and improvement of organizational performance measurement systems.i¾ i¾ It is described in this article.i¾ i¾ The approach and software emphasize identification of suppliers and customers, exogenous influences on organizational performance, the performance information infrastructure, and organizational components and processes.i¾ i¾ It requires detailed specification of performance measures and their logistical requirements.i¾ i¾ It supports analyses of individual metrics, sets of metrics sets, and the information infrastructure required for successful performance measurement.i¾ i¾ A case study illustrates use of the OPTIMAS process.