Stem cells and regenerative medicine

Daniel Mac Lloyd - Mind the Brain
Daniel Mac Lloyd

The most complex organ in humans is the brain and much about it is yet to be discovered. Ideally, researchers would directly study the human brain, but this is often technically or ethically impossible. Who would for instance be willing to undergo surgery to donate some nerve cells for research? Therefore, our scientists need to find alternative methods to study the brain. They have indirect ways to understand the mechanisms of our brain. For example by performing molecular analyses in patient samples that are easily accessible and more readily available, like blood or urine. There they can look for molecular changes linked to brain diseases. For other studies, they can use computational models, animal experiments in mice and zebrafish or nerve cell cultures.

In search for a model that mimics many features of the human brain, Prof. Jens Schwamborn and his team have developed a new 3D cell culture. They succeeded in turning human stem cells derived from skin samples into tiny, three-dimensional, brain-like cultures. These “mini-brain” or brain organoids behave very similarly to cells in the human midbrain, the part of the brain that degenerates in Parkinson’s disease. In the researchers’ petri dishes, different cell types develop, connect into a network, exchange signals and produce molecules typical of the active brain. By starting the culture with skin samples from individual patients, these organoids can be used to study the causes of Parkinson’s disease and how it could possibly be effectively treated.

In order to generate these ‘mini-brains’, skin cells have to be converted in the lab into pluripotent stem cells. Japanese researchers have won the Nobel Prize in 2012 for discovering for the first time molecular factors that can bring about this conversion. Their work has revolutionised cellular biology and opened new avenues for research at the LCSB. Once researchers have obtained pluripotent stem cells in the lab, they can potentially give rise again to any type of cell. By adding specific molecular factors, these stems cells can then be turned for instance into dopamine-producing nerve cells that are affected in Parkinson’s disease.
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Cerebral organoids: "mini brains" derived from pluripotent stem cells.

But which cellular factors need to be changed to induce the conversion from any kind of cell into another? This is the main research focus of Prof. Antonio del Sol Mesa and his team. Using computational modelling, they search for specific genes that characterise different cell types. Based on this knowledge, they can then design cocktails of chemical compounds that target the identified genes for cellular conversion and could ultimately be used for regenerative medicine. Recently, the LCSB researchers predicted molecular factors for the conversion of a type of heart cells into another. Their collaborators at Gladstone Institutes (US) have experimentally validated this prediction and show that, with Del Sol’s molecular cocktails, heart cells of the left ventricle could be turned into those of the right ventricle and vice versa. This discovery might have implications for the treatment of congenital heart diseases in the future. In collaboration with the Centre for Regenerative Medicine in Modena, Italy, the LCSB scientist are now trying to convert epithelial stems cells into corneal stem cells to ultimately treat patients whose eye has been damaged.

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Midbrain-specific organoids: two different types of "mini brains" derived from neural stem cells.

Stem cells and regenerative medicine

Daniel Mac Lloyd - Mind the Brain
Daniel Mac Lloyd

Stem cells

The most complex organ in humans is the brain and much about it is yet to be discovered. Ideally, researchers would directly study the human brain, but this is often technically or ethically impossible. Who would for instance be willing to undergo surgery to donate some nerve cells for research? Therefore, our scientists need to find alternative methods to study the brain. They have indirect ways to understand the mechanisms of our brain. For example by performing molecular analyses in patient samples that are easily accessible and more readily available, like blood or urine. There they can look for molecular changes linked to brain diseases. For other studies, they can use computational models, animal experiments in mice and zebrafish or nerve cell cultures.

Image
Cerebral organoids: "mini brains" derived from pluripotent stem cells.
In search for a model that mimics many features of the human brain, Prof. Jens Schwamborn and his team have developed a new 3D cell culture. They succeeded in turning human stem cells derived from skin samples into tiny, three-dimensional, brain-like cultures. These “mini-brain” or brain organoids behave very similarly to cells in the human midbrain, the part of the brain that degenerates in Parkinson’s disease. In the researchers’ petri dishes, different cell types develop, connect into a network, exchange signals and produce molecules typical of the active brain. By starting the culture with skin samples from individual patients, these organoids can be used to study the causes of Parkinson’s disease and how it could possibly be effectively treated.
Image
Midbrain-specific organoids: two different types of "mini brains" derived from neural stem cells.
In order to generate these ‘mini-brains’, skin cells have to be converted in the lab into pluripotent stem cells. Japanese researchers have won the Nobel Prize in 2012 for discovering for the first time molecular factors that can bring about this conversion. Their work has revolutionised cellular biology and opened new avenues for research at the LCSB. Once researchers have obtained pluripotent stem cells in the lab, they can potentially give rise again to any type of cell. By adding specific molecular factors, these stems cells can then be turned for instance into dopamine-producing nerve cells that are affected in Parkinson’s disease.

But which cellular factors need to be changed to induce the conversion from any kind of cell into another? This is the main research focus of Prof. Antonio del Sol Mesa and his team. Using computational modelling, they search for specific genes that characterise different cell types. Based on this knowledge, they can then design cocktails of chemical compounds that target the identified genes for cellular conversion and could ultimately be used for regenerative medicine. Recently, the LCSB researchers predicted molecular factors for the conversion of a type of heart cells into another. Their collaborators at Gladstone Institutes (US) have experimentally validated this prediction and show that, with Del Sol’s molecular cocktails, heart cells of the left ventricle could be turned into those of the right ventricle and vice versa. This discovery might have implications for the treatment of congenital heart diseases in the future. In collaboration with the Centre for Regenerative Medicine in Modena, Italy, the LCSB scientist are now trying to convert epithelial stems cells into corneal stem cells to ultimately treat patients whose eye has been damaged.