Interview: The art of cell culture for Parkinson’s

Parkinson’s disease is a neurodegenerative disease, which causes parts of the brain to degenerate. To elucidate the reasons why certain neurons die off and to develop new therapies, scientists in Luxembourg are carrying out research on the patients’ own cells. Kathleen Mommaerts, one of our assistant scientists, explains us how IBBL prepares primary material of the highest quality before the scientific work begins at the Luxembourg Centre of Systems Biomedicine (LCSB) of the University of Luxembourg.

Interview by Mélanie Moxhet

MM: Parkinson’s disease has been under the microscope for about a decade and, yet, it is still a mystery. Why is this novel approach bringing new hope for Parkinson’s patients and researchers?

KM: Basically, the approach focuses on the human midbrain, most particularly on the substantia nigra. This region of the brain is of considerable interest to researchers trying to better understand the mechanisms of the disease, since it is the location where neurons degenerate and trigger the motor symptoms seen in Parkinson’s, such as trembling and muscle stiffness. For obvious reasons, tissues of the substantia nigra cannot be resected from patients to be analysed in laboratories. An alternative solution that researchers from the LCSB successfully applied consists of growing midbrains derived from patients’ skin in a petri dish. These three-dimension structures behave like miniature brains and offer ideal conditions for testing new drugs.

MM: That is fascinating. Could you tell us more about the process? How do you turn human skin into functioning man-made brains?

KM: The process is the result of a collaboration between three Luxembourgish institutions. It all starts at the Parkinson’s Clinic of the Centre Hospitalier Luxembourg, where healthcare professionals extract a piece of skin tissue on a donor. Both Parkinson’s patients and healthy donors can take part in the study. Their participation is voluntary and strictly confidential. The skin biopsy, which is not widder than 5mm diameter, is then transported at room temperature to our laboratories, at IBBL. That’s when the “Cell culture Team” comes into play. Our job is to put the cells taken from the skin biopsies in culture and guarantee their multiplication. Our target is to multiply by a million the initial number of the cells, scientifically referred to as fibroblasts. After 3 months of culture, the multiplied fibroblasts are gradually frozen in liquid nitrogen at -196°C, putting them into a state in which they remain viable and available for research at any time in the future. The “magic” happens later at the LCSB. By adding a certain cocktail of chemicals to the fibroblasts, the researchers transform them into induced pluripotent stem cells. This cell type is able to produce any tissue of the body. In this particular case, they are triggered to differentiate into the neurons that affect the brain of Parkinson’s patients.

MM: What does cell culture implies? What is the optimal environment to grow skin cells?

KM: Cell culture is a long and delicate task. The cells are living organisms. They need to be fed, changed, cuddled and taken care of just like babies. Immediately after being taken from a patient, they are placed in a flask containing the nutrients that are essential to their survival and in an incubator at 37°C, body temperature. They cannot be left alone for long. No more than 3 days go by without checking on them. On top of that, it is essential to work in a sterile environment. The worst-case scenario would be the contamination of the fibroblasts in culture. That’s the reason why we work at all time under a microbiological safety hood. Our team is also trained properly and takes all the necessary protections to lower the risks. Actually, I am currently writing a PhD thesis about the optimisation of the fibroblast culture, trying to define the best ways to foster their multiplication and obtain cells of the highest quality.

MM: How often do you provide this service?

KM: We receive and process a maximum of five biopsies per week. The frequency depends on the patients, who put their trust in us and donate their samples for research. At the moment, we have already handled approximately 100. It is worth knowing that our collection at IBBL does not only include skin tissues. We also collect and make available blood, urine, saliva, cerebrospinal fluid and stool samples to biomedical researchers. In the case of neurodegenerative diseases, our biobank currently counts about 55,000 samples out of which 500 have already been used in research.

MM: Do you personally believe in the potential of using stem cells in research?

KM: In my opinion, pluripotent stem cells induced from patient cells are the future. They open new doors to brain research, but not only. Take organ transplantation. Let’s image that if a patient’s liver was about to fail, it could one day be possible to recreate the organ from a simple piece of the patient’s skin. In addition, as the transplant would be made from the patient’s own cells, it is less likely to be rejected by the body. The same applies to blood donation. If only we were able to produce blood in labs, there would be no more shortage. Honestly, I feel proud and lucky of being able to contribute to this exciting and promising project.

MM: Thank you very much Kathleen for taking the time to answer my questions, and good luck with your thesis!