Recent Trends in Research with Human Pluripotent Stem Cells: Impact of Research and Use of Cell Lines in Experimental Research and Clinical Trials

Summary: The human pluripotent stem cell (hPSC) research landscape is rapidly evolving. To assess possible novel trends in hPSC usage, we analyzed experimental hPSC research published from 2014 to 2016 and compared our data with those of earlier periods. The number of papers describing experimental work involving hPSCs increased further with clear differences in the scientific impact of publications from different countries. Our results confirm the leading position of US-based hPSC research, although to a lesser degree than observed previously. Our data reveal that research into human induced pluripotent stem cells alone surpassed human embryonic stem cell (hESC) research by 2015 and rapidly grew after that. We also report on continuing and even slightly growing research activities in the hESC field as well as on a generally declining rate of the generation of new hESC lines. An increasing portion of new hESC lines represents disease-specific and clinical-grade cell lines. The previously noted usage of only a few early established hESC lines in the vast majority of scientific work is sustained. We also provide a comprehensive overview on clinical trials on the basis of hPSCs. We find that the vast majority of those trials are based on hESC-derived cell products that were generated from an only limited number of relatively old cell lines. : Guhr et al. show that there are marked differences in the impact of recent hPSC research from different countries. The hESC line usage patterns remained mainly unchanged. The authors provide a comprehensive overview on clinical trials involving hPSC-derived cell products and find that these trials are mainly based on hESCs. Keywords: human pluripotent stem cells, human embryonic stem cells, human induced pluripotent stem cells, research, impact, citation frequencies, hESC lines, clinical trial

Advancing the Science of Developmental Neurotoxicity (DNT): Testing for Better Safety Evaluation

Developmental neurotoxicity is recognized by various stakeholders as an area that needs development of alternative tests to current animal testing guidelines. To address this need the 3rd International Conference on Alternatives for Developmental Neurotoxicity Testing (DNT3) was organized by the European Centre for the Validation of Alternative Methods (ECVAM). This conference discussed usefulness of alternative tools such as in vitro and non-mammalian test methods as well as in silico modeling for assessing the potential of chemicals to induce developmental neurotoxicity. Speakers presented evidence for the prevalence of developmental neurotoxicity associated with environmental chemicals. The participants of the conference also exchanged views about the science and policy aspects of DNT testing and pointed to the pressing need to develop a strategy, including specific criteria, for enabling the use of data produced by alternative test methods for assessing DNT hazards and risk assessment given that conventional test methods are costly and slow.JRC.I.2-Validation of Alternative Method

Reconsidering pluripotency tests: Do we still need teratoma assays?

AbstractThe induction of teratoma in mice by the transplantation of stem cells into extra-uterine sites has been used as a read-out for cellular pluripotency since the initial description of this phenomenon in 1954. Since then, the teratoma assay has remained the assay of choice to demonstrate pluripotency, gaining prominence during the recent hype surrounding human stem cell research. However, the scientific significance of the teratoma assay has been debated due to the fact that transplanted cells are exposed to a non-physiological environment. Since many mice are used for a result that is heavily questioned, it is time to reconsider the teratoma assay from an ethical point of view. Candidate alternatives to the teratoma assay comprise the directed differentiation of pluripotent stem cells into organotypic cells, differentiation of cells in embryoid bodies, the analysis of pluripotency-associated biomarkers with high correlation to the teratoma forming potential of stem cells, predictive epigenetic footprints, or a combination of these technologies. Each of these assays is capable of addressing one or more aspects of pluripotency, however it is essential that these assays are validated to provide an accepted robust, reproducible alternative. In particular, the rapidly expanding number of human induced pluripotent stem cell lines, requires the development of simple, affordable standardized in vitro and in silico assays to reduce the number of animal experiments performed