oa Editorial [Hot topic: Progress and Prospects of Human Pluripotent Stem Cell Research(Guest Editor: Chunhui Xu)]

Since the first report of human embryonic stem cells (hESCs) in 1998, the field of stem cell research has witnessed tremendous progress in many areas of both basic and pre-clinical studies. Notable examples include the identification of factors in controlling pluripotency of the cells, optimization of methods for derivation and cell growth, demonstrations of differentiation into various cell types, improvement of differentiation efficiencies, the proof-of-principle preclinical studies and preparation for clinical trials, and the discoveries of inducible pluripotent stem cells (iPSCs). This issue of Current Stem Cell Research and Therapy is devoted to the progress and prospects of several of these areas in human pluripotent stem cell research. Lin and Xu concentrate on the major achievements in the optimization of hESC culture conditions. Several exogenous regulators including growth factors and small molecules have been found to play critical roles in maintaining pluripotency for hESCs. These findings have guided the development of many animal-free and/or defined culture systems including human feeders and defined xeno-free media. In addition, they describe the attempts to derive and expand clinical-grade hESCs and their derivatives in large-scale culture systems for transplantation. Blin et al. provide a summary of current understanding on the cardiogenic transcriptional network and known factors involved in early cardiogenesis in vivo. This knowledge has contributed to the development of advanced protocols for efficient cardiac differentiation from hESCs. The authors also review the progress on the development of iPSCs and their cardiogenic potential and discuss challenges in the translation of iPSC research into clinical applications. Asai et al. first address issues in current cardiotoxicity testing during drug development and then propose the use of hESC/iPSC-derived cardiomyocytes for this application. They introduce in details a novel assay QTempo: a system to examine QT prolongation using cardiomyocytes derived from pluripotent stem cells. This method allows high throughput screening of drugs and may improve the accuracy of predictions of clinical cardiotoxicity. Hannoun et al. focus on the differentiation of hepatic endoderm (HE). They review human liver biology and how this knowledge can be translated into the development of differentiation protocols to yield HE from hESCs. They also speculate a role for oxygen tension as a new regulatory mechanism in HE differentiation and highlight the importance of mitochondrial function in HE generation. Islam et al. present an example of how hESCs can be used in basic studies in human developmental biology. They illustrate the niche microenvironment for adult hematopoiesis and emphasize the potential of developing hematopoietic stem cells and niche components such as endothelial, osteoblast and osteoclast populations from hESCs for the study of their cellular and molecular interactions. The article by Dodla et al. provides an overview on the role of various factors including glial cells, glial and neuronal derived factors and cell adhesion molecules on the formation of functional synapses in neuronal cultures in vitro. They then discuss how these can be applied to derive functionally active hESC-derived neural networks, a particularly challenging goal yet to be achieved using current technology. The final article contributed by Levengood and Murphy focuses on biomaterials for the establishment of high-throughput stem cell culture screening system. They advocate this technology for the investigation of the effect of the complexity of the stem cell's microenvironment, such as interaction with cells, matrix and soluble factors, on cell growth and differentiation. hESCs and human iPSCs have unlimited proliferative capacity in the undifferentiated state while maintaining their pluripotency to develop into multiple cell types. Understanding the many aspects of stem cell biology will be critical to fully realize the potential of these cells. Progress described above and much more elsewhere will help pave the way to reaching the goals of utilizing these cells as model systems to study human developmental biology, physiologically relevant materials useful for drug development, and regenerative medicine to treat numerous diseases such as spinal cord injuries and other neurodegenerative diseases, cardiovascular disease, diabetes and liver disease.