RESEARCH PAPER New Biotechnology  Volume 32, Number 1  January 2015 Application of human induced pluripotent stem cells for modeling and treating neurodegenerative diseases Natalie L. Payne 1 , Aude Sylvain 1 , Carmel O’Brien 2,3 , Daniella Herszfeld 1 , Guizhi Sun 1 and Claude C.A. Bernard 1 1 Australian Regenerative Medicine Institute, Monash University, Victoria 3800, Australia 2 CSIRO, Materials and Science Engineering, Victoria 3800, Australia 3 Department of Anatomy and Developmental Biology, Monash University, Victoria 3800, Australia The advent of human induced pluripotent stem cells (hiPSCs), reprogrammed in vitro from both healthy and disease-state human somatic cells, has triggered an enormous global research effort to realize personalized regenerative medicine for numerous degenerative conditions. hiPSCs have been generated from cells of many tissue types and can be differentiated in vitro to most somatic lineages, not only for the establishment of disease models that can be utilized as novel drug screening platforms and to study the molecular and cellular processes leading to degeneration, but also for the in vivo cell-based repair or modulation of a patient’s disease profile. hiPSCs derived from patients with the neurodegenerative diseases amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis have been successfully differentiated in vitro into disease-relevant cell types, including motor neurons, dopaminergic neurons and oligodendrocytes. However, the generation of functional iPSC-derived neural cells that are capable of engraftment in humans and the identification of robust disease phenotypes for modeling neurodegeneration still require several key challenges to be addressed. Here, we discuss these challenges and summarize recent progress toward the application of iPSC technology for these four common neurodegenerative diseases. Introduction The incidence of neurodegenerative diseases is expected to rise dramatically as life expectancy increases, representing a significant economic and social burden. While current treatments can alle- viate some symptoms, they are generally ineffective at halting disease progression across most neurodegenerative diseases. The development of therapies that can prevent the accumulation of neurological deficits has been hampered by several factors, includ- ing our lack of understanding of disease pathogenesis, inability to link genetic and environmental influences with changes in central nervous system (CNS) function, limited access to tissue samples representative of early pathology, and animal models that do not completely recapitulate all aspects of the disease. The ability to reprogram mouse somatic cells into induced pluripotent stem cells (iPSCs) by the introduction of four embryo- nic transcription factors first published by Yamanaka and collea- gues [1], was quickly followed by the successful reprogramming of human somatic cells from both healthy [2,3] and diseased indi- viduals [4,5]. This has sparked a tremendous global effort to realize autologous cell-based treatments for a wide spectrum of degen- erative disease profiles. It is projected that cells sourced directly from a patient with informed consent to generate human (h)iPSCs will then be differentiated in vitro to relevant somatic lineages, for both the assessment of appropriate pharmacological management of the patient’s disease symptoms and ultimately for the in vivo Research Paper Corresponding author: Bernard, Claude C.A. (claude.bernard@monash.edu) www.elsevier.com/locate/nbt http://dx.doi.org/10.1016/j.nbt.2014.05.001 212 1871-6784/ß 2014 Published by Elsevier B.V.