ABSTRACT
The last 5 years have witnessed a significant increase in the number of clinical studies based on human pluripotent stem cells (hPSCs). In parallel, concern is increasing about the proliferation of unregulated stem cell treatments worldwide. Regulated clinical testing is a de facto standard to establish the safety and efficacy of new cell therapies, yet reliable information on clinical studies involving hPSCs is scattered. Our analysis of a multitude of resources found 54 clinical studies involving several types of hPSCs, which are performed in ten countries. While the majority of those studies is based on human embryonic stem cells (hESCs), clinical studies involving human induced pluripotent stem cells increased more strongly in the past 2 years than the number of hESC-based studies. A publicly accessible database was created using the human pluripotent stem cell registry (https://hpscreg.eu) platform, providing a steadily updated comprehensive overview on hPSC-based clinical studies performed worldwide.
Subject(s)
Data Curation , Databases as Topic , Induced Pluripotent Stem Cells/cytology , Cell Line , Clinical Trials as Topic , Human Embryonic Stem Cells/cytology , Humans , Time FactorsABSTRACT
Chinese herbal medicines (CHMs) have been widely used during pregnancy, but feto-embryo safety tests are lacking. Here we evaluated in vitro embryotoxicity tests (IVTs) as alternative methods in assessing developmental toxicity of CHMs. Ten CHMs were selected and classified as strongly, weakly and non-embryotoxic. Three well validated IVTs and prediction models (PMs), including embryonic stem cell test (EST), micromass (MM) and whole embryo culture (WEC), were compared. All strongly embryotoxic CHMs were predicted by MM and WEC PM2. While all weakly embryotoxic CHMs were predicted by MM and WEC PM1. All non-embryotoxic CHMs were classified by EST, MM, but over-classified as weakly embryotoxic by WEC PM1. Overall predictivity, precision and accuracy of WEC determined by PM2 were better than EST and MM tests. Compared with validated chemicals, performance of IVTs for CHMs was comparable. So IVTs are adequate to identify and exclude embryotoxic potential of CHMs in this training set.
Subject(s)
Drugs, Chinese Herbal/toxicity , Embryo, Mammalian/drug effects , Embryonic Stem Cells/drug effects , Teratogens/toxicity , Toxicity Tests/methods , Animals , Blastocyst Inner Cell Mass/drug effects , Blastocyst Inner Cell Mass/metabolism , Blastocyst Inner Cell Mass/pathology , Cell Differentiation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/classification , Embryo, Mammalian/metabolism , Embryo, Mammalian/pathology , Embryonic Development/drug effects , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/pathology , In Vitro Techniques , Mice, Inbred ICR , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Predictive Value of Tests , Rats, Sprague-Dawley , Sensitivity and Specificity , Teratogens/classificationABSTRACT
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.
