Arturo Alvarez-Buylla, University of California, San Francisco, USA
Oliver Brüstle , University of Bonn, Germany
Pete Coffey, University College London, UK
Gianvito Martino, San Raffaele Scientific Institute, Milan, Italy
Anders Björklund, University of Lund, Sweden
Lorenz Studer, Memorial Sloan Kettering Cancer Center, New York, USA
Hynek Wichterle, Columbia University, New York, USA
A number of neurological diseases are characterized by the loss of individual neuronal subtypes and/or specialized glial cells. The ongoing effort is to understand the underlying pathophysiology in an attempt to identify suitable drug targets. Opportunities have emerged within the stem cell field. Unprecedented advances have been made in our understanding of stem cells and through them much can be learned about the physiology and pathophysiology of the cells that degenerate in different brain disorders with the ultimate goal of delivering therapeutically relevant stem cells that could ameliorate the clinical outcome. The Course will bring together a collection of investigators who are at the forefront of their field and will showcase research at the frontiers of neural stem cells for neurorepair.
Stem cells exist in the developing and adult nervous system and are able to generate neuronal and glial cells both in vivo and in vitro. The first focus of the Course will be to familiarize participants with the early results that have led to the identification, characterization, and isolation of neural stem cells. The data that clarify the nature of the neural stem cell niche will also be discussed. Specific aspects of human brain development that are relevant for directing stem cells into specific neuronal and glial fates will be analyzed with highlights on recent novel important perspectives. Critical in these strategies is knowledge of the intimate developmental mechanisms contributing to the generation of the different cell types of the nervous system in vivo and the possibility to implement them in vitro.
Another major focus will be the potential of human pluripotent stem cells as a source of neurons and glial cells for mechanistic, transplantation and drug screening approaches. The Faculty members are the investigators who have pioneered the very first attempts at generating specialized neurons from human embryonic stem (ES) cells. They have also identified alternative scalable sources of neural progenitors. Accordingly, human ES and induced pluripotent stem (iPS) cell-derived neural stem cell populations have been obtained which can be expanded to homogeneity, while retaining the capacity to mature into functional neurons. The participants will hear these data first-hand from the leading investigators actively involved in cutting-edge research and stress will be placed on the most recent achievements obtained with human iPS/directly reprogrammed cells for neurological diseases.
Many other emerging features of the stem cell field will be object of analysis and discussion throughout the Course. For example, recent discoveries have identified transcription factors and morphogens critical for successful phenotype specification and differentiation of therapeutically relevant dopaminergic and striatal medium sized spiny neurons from human pluripotent stem cells. Distinct subtypes of motor neurons can also be derived from ES/iPS cells, allowing the study of the mechanisms that regulate the growth of motor axons towards their specific targets. These studies will be discussed in the context of the current attempts at developing stem cell-based models and therapies for diseases such as Parkinson's and Huntington's disease, amyotrophic lateral sclerosis and spinal muscular atrophy.
One emerging avenue of research under intense investigation is the systemic or intracerebral delivery of neural stem and progenitor cells or their endogenous activation in an attempt to develop potential treatments for diseases such as multiple sclerosis and stroke. These studies will be discussed extensively and the evidence of an unexpected cross-talk between neural stem cells and immune cells in the nervous system will be presented: this specific aspect represents a very promising key to better brain repair.
Despite public hope that stem cells -and especially adult stem cells- may be the cure for many (if not all) diseases, in reality it is very well possible that evidence supporting their use will be obtained for only a limited number of conditions. In the face of such high expectations it is the precise responsibility of the scientific community that only results of rigorously conducted preclinical studies are transferred to the clinic through a rigorous evidence-based translational approach. A wealth of such evidence obtained in animals in the '90s has lead to the first clinical trials in Parkinson's disease using grafts of fetal dopaminergic progenitors. These studies have demonstrated that effective repair can be achieved by neural transplantation: evidence and knowledge acquired from these early studies and from more recent transplantation trials in Parkinson's disease will be reviewed with dedicated attention to the current status quo. Also, the most recent phase I and phase II trials in macula degeneration using hES cell-derived retinal cells will be reviewed.
It is important in this respect to consider that the development of clinically competitive stem cell therapies for neurological disorders is requiring more time and efforts than anticipated. The Faculties will thoroughly discuss the specific puzzles, paradoxes and conflicts that stem cell research poses in an open atmosphere and novel perspectives will be highlighted.
The Course will provide participants with a thorough understanding of the identity, properties, location and characteristics of growth and differentiation of pluripotent stem cells and multipotent neural stem cells. Participants will also have the opportunity to acquire more in depth knowledge of novel, cutting-edge approaches and technologies now available to derive specific human cell types of the nervous system.
In all sections of the Course, a strong emphasis will be placed on critical analysis to provide not only a thorough understanding of the great potential but also of the difficulties and pitfalls present in this highly sensitive field. Participation in the Course will not only provide an essential conceptual and methodological framework for anyone intending to pursue rigorous research but will also build the foundation for maintaining the high standards and the ethical dimension that are necessary in order to translate validated research findings into new regenerative therapies for presently incurable diseases.