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Brain tissue from a petri dish

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Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have succeeded in turning human stem cells derived from skin samples into tiny, three-dimensional brain-like cultures that behave very similarly to cells in the human midbrain. In the researchers' petri dishes, different cell types develop, connect into a network, exchange signals and produce metabolic products typical of the active brain.

"Our cell cultures open new doors to brain research," said Jens Schwamborn, Ph.D., a professor in developmental and cellular biology at LCSB and a lead investigator on the study, which appeared recently in Stem Cell Reports. "We can now use them to study the causes of Parkinson's disease and how it could possibly be effectively treated."

The human midbrain is of particular interest to Parkinson's researchers as it is the seat of the tissue structure known medically as the substantia nigra. Here, nerve cells – specifically dopaminergic neurons – produce the messenger dopamine. Dopamine is needed to maintain smooth body movements. If the dopaminergic neurons die off, then the person affected develops tremors and muscle rigidity, the distinctive symptoms of Parkinson's disease. For ethical reasons, researchers cannot take cells from the substantia nigra to study them. Research groups around the world are therefore working on cultivating three-dimensional structures of the midbrain in petri dishes.

The LCSB scientists worked with induced pluripotent stem cells (iPSCs) – stem cells that cannot produce a complete organism, but can be transformed into all cell types of the human body. The procedures required for converting the stem cells into brain cells were developed by Anna Monzel as part of her doctoral thesis, which she is doing in Dr. Schwamborn's group. "I had to develop a special, precisely defined cocktail of growth factors and a certain treatment method for the stem cells, so that they would differentiate in the desired direction," Monzel said of her approach. To do this, she was able to draw on extensive preparatory work that had previously been done in Dr. Schwamborn's team. The pluripotent stem cells in the petri dishes multiplied and spread out into a three-dimensional supporting structure, producing tissue-like cell cultures.

"Our subsequent examination of these artificial tissue samples revealed that various cell types characteristic of the midbrain had developed," Dr.  Schwamborn said. "The cells can transmit and process signals. We were even able to detect dopaminergic cells, just like in the midbrain.

"On our new cell cultures, we can study the mechanisms that lead to Parkinson's much better than was ever the case before,” he added. “We can test what effects environmental impacts such as pollutants have on the onset of the disease, whether there are new active agents that could possibly relieve the symptoms of Parkinson's or whether the disease could even be cured from its very cause. We will be performing such investigations next."

Learn more:

https://www.eurekalert.org/pub_releases/2017-04/uol-btf041317.php
DOI: 10.1016/j.stemcr.2017.03.010