Glial progenitor cell transplantation and the generation of chimeric animal models with human brain cells: implications for novel therapeutics

Abstract

Background: The potential of exogenous stem cell or progenitor cell transplantation as a novel therapeutic strategy to address unmet medical needs is a vast and important area of investigation. A recent US patent has been issued to Goldman from the University of Rochester based on pioneering studies with human fetal and adult-derived glial progenitor cells (GPCs), covering the generation of chimeric mouse/human animals. Objective/method: In this patent and associated manuscript, extensive chimerism due to grafting of human GPCs is associated with remyelination and functional rescue of mice congenitally deficient in oligodendrocyte survival and myelination, due to a deletion in the myelin basic protein gene (the shiverer mouse). This review highlights the implications of generating human/mouse chimeric animals for the study of human brain physiology, preclinical studies and the clinical application of progenitor cells towards the development of novel therapeutics for the treatment of demyelinating disorders. Conclusion: The use of GPCs offers promise for remyelination disorders, and the ability of these cells to repopulate the entire rodent nervous system should allow for the investigation of the physiological properties of human glial derivatives in an in vivo context, enhancing the understanding of mechanisms with a primary effect through the modulation of human glial cell biology.