Stem cell technology for neurodegenerative diseases

Abstract

Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

Figure 1. Analysis of the current state of stem cell research for neurodegenerative diseases

A. Comparison of approximate number of affected individuals in the USA (blue) and anticipated breakdown of NIH spending on diseases in 2011 (green). B. Portion of published literature focusing on stem cell technologies for individual neurodegenerative diseases overall (blue) and between 2006 and 2010 (green). Literature mining was performed using the MeSH terms “Alzheimer disease”, “Parkinson disease”, “Huntington disease”, “amyotrophic lateral sclerosis”, “Muscular atrophy, spinal” and “stem cell”. C. NIH spending on stem cell technologies in 2006 and 2011 by stem cell type and species.

Figure 2. Stem cell technology and cellular therapy classifications

Cellular therapy involves the treatment of diseases using cells or tissue grafts. Various types of stem cells may be utilized, each possessing unique characteristics and advantages depending on the desired outcomes. Selecting the appropriate stem cell and treatment mechanisms for each disease is necessary to support the translation of cellular therapies for neurodegenerative diseases from bench to bedside. Solid arrows represent divisions within each category. Dashed arrows represent sources of iPS cells and NPCs.

Figure 3. Translating a stem cell-based treatment for ALS from the bench to patients

Overview of the stages involved in translating a stem cell therapy from the bench to patients, using the current ALS stem cell trial as a representative timeline. Supporting studies began in the late 1990’s with the development of the HSSC line utilized in the trial and transitioned from HSSC characterization, through validation in animal models and stages required for human applications^{, , ,} , and finally to clinical trial approval in 2009^{, -}. The timeline in this figure reflects over a decade of preclinical supporting studies for the current ALS trial. This road map provides an outline of the rigorous stages required for the translation of stem cell therapies from the bench to bedside that may be applied to multiple neurodegenerative diseases.