Abstract
The first derivation of human embryonic stem cells brought with it a clear understanding that animal models of human disease might be replaced by an unlimited supply of human cells for research, drug discovery, and drug development. With the advent of clinical trials using human pluripotent stem cell-based therapies, it is both timely and relevant to reflect on factors that will facilitate future translation of this technology. Human pluripotent cells are increasingly being used to investigate the molecular mechanisms that underpin normal and pathological human development. Their differentiated progeny are also being used to identify novel pharmaceuticals, to screen for toxic effects of known chemicals, and to investigate cell or tissue transplantation strategies. The intrinsic assumption of these research efforts is that the information gained from these studies will be more accurate, and therefore of greater relevance, than traditional investigations based on animal models of human disease and injury. This review will therefore evaluate how animals and animal-derived products are used for human pluripotent stem cell research, and will indicate how efforts to further reduce or remove animals and animal products from this research will increase the clinical translation of human pluripotent stem cell technologies through drug discovery, toxicology screening, and cell replacement therapies.
Highlights
Human pluripotent stem (PS) cells are providing a plentiful supply of differentiated human cell types for developmental biology, drug discovery, and clinical applications
Given the time and financial costs associated with animal models, as well as the fact that they often do not accurately predict the toxicity or efficacy of new treatments and products in humans [3,4,5], it is timely to analyse the various fields of human PS cell research while keeping in mind the 3R principle of ethical animal use in research: to reduce, replace, or refine animal usage [6]
The potential for human PS cells to increase our understanding of human development and to provide differentiated cells for drug screening, toxicology studies, and cell replacement therapies is widely acknowledged
Summary
Human pluripotent stem (PS) cells are providing a plentiful supply of differentiated human cell types for developmental biology, drug discovery, and clinical applications. Xeno-free human pluripotent stem cell characterisation Replacing the teratoma assay will require the establishment of methods that comprehensively and quantitatively define a broad range of phenotypic and functional parameters characteristic of pluripotent cells Attempts to do this via genome-wide expression profiling of undifferentiated human ES and iPS cells has led to in silico methods, such as PluriNet [22], which can catalogue and compare the gene expression profiles of newly derived cell lines. Other studies questioned the extent of Neu5Gc contamination in human ES cell cultures and its immunogenic potential [57,58,59], significant efforts continue to be made to enable animal product-free culture of human pluripotent cells and their derivatives As mentioned above, this has led to the development of a variety of animal product replacements including human feeder cells [15], defined media [7], and chemical or recombinant extracellular matrices [17]. These studies will aid the clinical translation of a wider variety of human PS cell-derived cell types
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
