A research team led by the University of Coimbra was able to generate human stem cells from skin cells, which have shown to have long-term therapeutic potential for the Machado-Joseph disease, a rare condition with a high prevalence in Portugal. This research paves the way for the development of cells that could be used to treat this neurodegenerative disease, which affects movement and speech.
In the scientific article Graft-derived neurons and bystander effects are maintained for six months after human iPSC-derived NESC transplantation in mice's cerebella - published in the journal Scientific Report, of the Nature group - the research team "shows that it is possible to create stem cells from cells extracted from people with Machado-Joseph disease with therapeutic potential", explains Liliana Mendonça, researcher at the Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC) and the Center for Innovation in Biomedicine and Biotechnology (CIBB).
"Our discovery demonstrates the feasibility of applying personalized therapies to people with this disease, by creating stem cells from the patients we intend to treat, which will result in greater acceptance of the transplant," adds the study leader. Stem cells are extremely versatile and can give rise to specialized cells from various tissues and organs in the human body.
Machado-Joseph disease is a currently untreatable condition, with the cerebellum being one of the most affected regions of the brain. It is characterized by extensive neuronal death, difficulties with motor coordination, swallowing and speech. "It has a high prevalence in the Azores, especially on the island of Flores, which has the highest incidence of the disease worldwide," says the UC researcher.
To achieve this result, the research team created cells that proved capable of giving rise to neurons in cell cultures (a set of techniques for testing the behavior of cells in an artificial environment) and also in cerebral organoids (tissues generated in vitro, i.e. outside of living organisms, which simulate human neurodevelopment by functioning as "mini-brains").
At the same time, "in this study we also observed that the human stem cells survived up to six months after transplantation into the cerebellum of the animal model, having differentiated into glia cells [cells of the central nervous system that perform various functions, namely supporting neurons] and neurons", says Liliana Mendonça. This means that these cells have the potential to act positively in controlling neurodegenerative diseases.
With this research, the team sought to chart new paths for the development of treatments for a rare and highly disabling disease. "There is a great need to develop therapeutic strategies that can treat neurodegenerative diseases, which robustly improve the quality of life of patients, thus contributing to reducing the health burden on health systems and the families of these patients," says the researcher.
The work carried out by the CNC-UC Gene and Stem Cell Therapies for the Brain Research Group team - coordinated by the president of CNC-UC, CIBB coordinator and professor at the UC Faculty of Pharmacy (FFUC), Luís Pereira de Almeida - is now being further developed, namely to study how these cells can improve the disease's motor coordination problems, using an animal model. The scientists are also going to "develop strategies to improve the migration of the cells and then their differentiation into cerebellar neurons, after their transplantation into the brain, something that could significantly increase the therapeutic effects of these cells", the research coordinator points out.
Other researchers from the University of Coimbra also took part in the study: Luís Pereira de Almeida, Daniel Henriques (CNC-UC and CIBB), Vanessa Fernandes (CNC-UC), Ricardo Moreira (FFUC, CNC-UC and CIBB), João Brás (CNC-UC) and Sónia Duarte (CNC-UC and CIBB). The research also included the collaboration of Jens C. Schwamborn, a researcher at the Center for Systems Biomedicine in Luxembourg.
The scientific article is available here.
Catarina Ribeiro and Liliana Mendonça
