Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Analysis of Olfaction after Bilateral Nasoseptal Rescue Flap Transsphenoidal Approach with Olfactory Mucosal Preservation.

OBJECTIVE: To ascertain the impact of septal olfactory strip preservation and bilateral rescue flap elevation on the incidence of olfactory dysfunction. STUDY DESIGN: Case series with chart review of patients undergoing endoscopic endonasal skull base surgery (2012-2014). SETTING: Providence Saint John\u27s Health Center and John Wayne Cancer Institute. SUBJECTS AND METHODS: The incidences of postoperative epistaxis, hyposmia, and anosmia were analyzed using the Brief Smell Identification Test (B-SIT), which was completed in 110 of the 165 patients. RESULTS: Seventy-eight patients required extended approaches. Bilateral nasoseptal rescue flaps were elevated in 144 patients (87.3%) and pedicled nasoseptal or middle turbinate flaps in 21 patients (12.7%). The neurovascular pedicles were preserved in all patients, and there were no episodes of postoperative arterial epistaxis. Normal olfaction was noted in 95 patients (86%), with new hyposmia noted in 5 patients (5.5%). Within the rescue flap cohort, new hyposmia occurred in 6.3% ( CONCLUSIONS: Superior olfactory strip preservation during elevation of reconstructive flaps preserves olfactory function and maintains adequate surgical exposure. In addition, rescue flaps have significantly diminished the rate of arterial postoperative epistaxis while maintaining the ability to harvest nasoseptal flaps for future reconstruction