2 research outputs found
Pluripotent stem cells as a model to study non-coding RNAs function in human neurogenesis
No full textAs fine regulators of gene expression, non-coding RNAs, and more particularly micro-RNAs (miRNAs), have emerged as key players in the development of the nervous system. In vivo experiments manipulating miRNAs expression as neurogenesis proceeds are very challenging in the mammalian embryo and totally impossible in the Human. Human pluripotent stem cells (hPSC), from embryonic origin (hESC) or induced from adult somatic cells (iPSC), represent an opportunity to study the role of miRNAs in the earliest steps of human neurogenesis in both physiological and pathological contexts. Robust protocols are now available to convert pluripotent stem cells into several sub-types of fully functional neurons, recapitulating key developmental milestones along differentiation. This provides a convenient cellular system for dissecting the role of miRNAs in phenotypic transitions critical to brain development and plasticity that may be impaired in neurological diseases with onset during development. The aim of this review is to illustrate how hPSCS can be used to recapitulate early steps of human neurogenesis and summarize recent reports of their contribution to the study of the role of miRNA in regulating development of the nervous system
Intracerebral transplantation for neurological disorders. Lessons from developmental, experimental and clinical studies
No full textThe use of human pluripotent stem cells for cell therapy faces a number of challenges that are progressively answered by results from clinical trials and experimental research. Among these is the control of differentiation before transplantation and the prediction of cell fate after administration into the human body, two aspects that condition both the safety and efficacy of the approach. For neurological disorders, this includes two steps: firstly, the identification of the optimal maturation stage for transplantation along the continuum that transforms pluripotent stem cells into fully differentiated neural cell types, together with the derivation of robust protocols for large-scale production of end-products, and, secondly, the understanding of environmental cues that will allow maintenance of commitment and avoid the development of adverse structures. This review will summarize our knowledge on developmental processes that have been applied to achieve robust in vitro differentiation of pluripotent stem cells into neural progenitors, and will examine the effects of the recipient brain environment on the pre-transplantation commitment
