We recently featured the review ‘Utilization of stem cells to model Parkinson’s disease – current state and future challenges’ from our partner journal, Future Neurology. Here, the article’s co- author, Jens Schwamborn from the University of Luxembourg, Luxembourg, gives us some background on his research and the recent article.
First, please could you tell us a little about your research background and what led you to become interested in regeneration in Parkinson’s disease (PD)?
As a student in biochemistry, I was already interested in brain research. Luckily I had the opportunities to follow this interest and focus my research in the neuroscience area. I became interested in PD in 2009 when setting up my first independent group. My aim was exploring how stem cells could be used for regenerative approaches. PD was the ideal model to explore this concept. I am convinced that the ability to age in dignity is one of the central challenges that aging societies face. Therefore, research that addresses age-associated neurodegenerative disorders is of utmost importance from my point of view.
Please could you give us an overview of your recent paper, ‘Utilization of stem cells to model Parkinson’s disease – current state and future challenges’?
In this manuscript we review current approaches, based on the utilization of human patient specific induced pluripotent stem cells (iPSCs), for in vitro modeling of PD. The field of in vitro disease modeling grew dramatically with the advent of iPSCs. In the manuscript we highlight how iPSCs are currently used and the findings that have be obtained. There, we focus particularly on mutations in the gene LRRK2 that are known to be associated with PD. Although mutations in several genes are associated with PD, we decided to focus on LRRK2 because this is most probably the best studied gene in this context.
Besides describing what has been achieved already, we tried to highlight current limitations and have a look at emerging technologies in this field. In particular, the rapid progress with the CRISPR/Cas9 system and the appearance of more complex brain organoid models have the potential to strongly accelerate the field of PD in vitro disease modeling.
What do you see as the key limitations in the field of in vitro disease modeling?
Often, studies are based on relatively few patient-specific iPSC lines, so the availability of more lines would certainly help us to get a more comprehensive picture of the disease. Unfortunately, the sharing of patient-specific iPSCs is still not so easy. Most researchers are very willing to share the lines, but administrative processes slow down the whole process dramatically. Having easy access to a comprehensive library of disease-specific lines would be a huge step forward.
Another limitation is that we try to model an age-associated disease with relatively young neurons. Therefore, further refined methods for in vitro aging are needed. On the other hand, we follow the hypothesis that PD is actually a neurodevelopmental disorder, or at least has a strong neurodevelopmental component. If that’s correct, using iPSC-derived cell types might be well justified.
Looking ahead, where do you hope the field will be in the next 5–10 years?
That’s always an ingrate question for a researcher, because we should be careful not to promise too much. However, I am convinced that particularly the development of complex in vitro human brain models (brain organoids) will help us significantly in understanding PD. I guess that in 5–10 years we will have come to a more personalized approach, where we will see the term Parkinson’s disease more as an umbrella term. I think personalized medicine will be one of the major revolutions that we are going to experience in the next years.