About this Research Topic
In recent years there has been a renewed interest on understanding the molecular basis of neurological diseases whose phenotypes are present in early stages of development and childhood. The unprecedented access to sophisticated tools of molecular biology and genetics has allowed for a better understanding of these diseases, including developmental malformation, microcephaly, autism spectrum disorders, Down syndrome, and early onset zika related-microcephaly among others.
New development in genetic technologies have revolutionized the way that these diseases are studied, including novel techniques of cellular reprogramming that permit the generation of patient-derived cells, such as inducible pluripotent stem cells (iPSCs), to model the molecular and cellular mechanisms that underlie the pathology of these diseases. In addition, to advance our understanding there is also opportunities to understand the impact of evolutionary forces on the normal human brain development.
All this new knowledge has been possible by the utilization of new stem cells platforms that are ex-vivo cell cultures techniques to recapitulate the disease process in a personalized manner. There are multiple stem cell based techniques for modeling disease including both two and three-dimensional (2D & 3D) approaches. In particular 3D organoid cultures have shown the extraordinary ability to replicate the early stages of human development. Therefore, stem cell derived neural models, allow us to recapitulate and dissect early human fetal neuronal development that would be otherwise inaccessible. Despite, all these advances there are significant challenges and roadblocks to utilize stem cell platforms as a robust translational tool to understand the pathogenesis of neurodevelopmental disorders and the identification of novel therapeutic targets.
As editors, we have contributed to the field of stem cells in the understanding of early stages of neural stem cells development and microcephaly, the responses of neural stem cells (NSCs) to injury, the utilization of patient derived cells to model neurogenetic disorders and in vivo modeling of neuronal pathology in neurodevelopmental diseases.
In this supplement, we propose to address with the help of our contributors, the most significant and challenging questions remaining in this exciting field to date. We will attempt to bring contributors that will include 2D and 3D stem cell platforms and that will address the following topics:
1) The use of inducible patient derived stem cells to study human development in vitro and in vivo, technical developments
2) The use of organoids to model early stages of brain organogenesis, limitation, self-organization, differentiation, and disease
3) Development of organoids with vasculature to overcome restriction in size in the organoids and expand human neural development in vitro
4) ELSI (ethical, legal, societal issues) issues related to developing self-organized human brain tissue in vitro from patients, especially the formation of limited neural circuits and the emergence of limited neural connectivity
5) Modeling brain connectivity in organoids
6) Phenotypes and genotypes correlation of stem cells models of neurogenetic disorders
7) Modeling complex neurogenetic disorders that involve immunity in the CNS. Aicardi Goutierres syndrome, Nasu-Hakola, leukodystrophies
8) Modeling the role of adaptive and non-adaptive immunity on neurodevelopmental disorders, including autism, Zika virus infection
9) Clinical translational studies currently based on findings accomplished with stem cells derived neural models
We hope to address the most significant issues in the field and produce an authoritative supplement that will be used by all the readership of Frontiers.
Keywords: neurogenic disorders, inflammatory neurodevelopmental disorders, neurological disease, neural models
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.