H2020Индивидуална стипендия2019–2023

STRELECOID · Stretchable mesh-electrodes interfacing human iPSC brain organoids

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период
2019-12-01 → 2023-07-19
Финансиране от ЕС
246 669 €
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3
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MSCA-IF

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Накратко на български

Стволови клетки от кожа или кръв се използват за създаване на тъкан от човешки мозък в лаборатория, за да се изследват заболявания като епилепсията. Това позволява изучаване на електрическата активност на невроните и тестване на терапии без риск за пациента.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Stretchable mesh-electrodes interfacing human iPSC brain organoids

Human induced pluripotent stem-cells are a technology which allows to take a piece of human skin or a bit of blood, and turn that tissue into stem cells. Stem cells have the particularity of being able to become any cell in the human body given the correct environment, e.g tissues like lung, heart, liver, brain etc. It is therefore possible to take a bit of the patient's skin or blood and create a piece of brain tissue in the petri dish, by making the stem cells generated from the patient's skin or blood, turn into neurons, the cells which make up the brain. This is very advantageous because it is unfeasible to perform experiments on human's brain as it would involve opening up the skull and perform experiments which may not fail due to ethical and safety concerns. Using human induced pluripotent stem cells allows one to duplicate real, human neural tissue outside of the patient's body. In the case that this patient carries a genetic neuropsychiatric disorder like certain kinds of epilepsies, one can create a multiple copies of the afflicted brain tissue and study therapeutic approaches on it without risking to harm the patient. This constitutes a paradigm shift in studying human neuropsychiatric disorders and opens the door not only for therapeutics but also personalized medicine. Many neuropsychiatric disorders are characterized by abnormal electrical activity of the neurons making up the brain tissue. One therefore needs means of measuring such electrical activity. These neural tissues which we call organoids do not possess an immune system or a blood vessel network. Therefore, one cannot insert instruments and create tissue damage without inducing the death of the entire organoid, as it is incapable of shuffling out cell debris from itself. A possibility to circumvent the insertion of an electrical measuring device is to have the organoid proliferate and grow on top of a device and create a sort of symbiote: organoid and electrode-array. To minimize mechanical mismatch, which could lead to inflammation of the tissue, and to make the measuring device as imperceptible as possible to the neurons making up the organoid, it is important to reduce the footprint of the measuring device as much as possible while making it able to deform and reshape itself under the strain impacted by growing cells. To fulfill these characteristics, I develop mesh-electrode-arrays akin to fishnets which have a very low footprint and are able to deform and reconfigure their shapes when exposed to external stresses imposed by the cells. Cells can then grow freely around this mesh-electrode-array and incorporate it into themselves on the long term. In this way, the measurement device is constantly inside the organoid and no insertion needs to ever happen. Because this paradigm allows for continuous monitoring of cellular activity, we envision to couple the mesh-electrode-array with learning algorithms that over time figure out how to, for example, send in small electrical stimuli through various electrodes in order to disrupt epileptic seizures in such organoids. Hopefully, such therapeutic approaches can then be translated to humans in the form of implantable devices.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Recent advances in cellular engineering allow to recruit skin cells from donors and reprogram them into neural stem cells. These induced pluripotent stem cells (iPSC) bear the genetic code of the human patient. Efforts to culture these cells in-vitro have been successful in creating a wide variety of 3D arrangements called neurospheres. Because the human central nervous system is by and large inaccessible at all developmental stages, these functional tissue preparations are invaluable. Furthermore, clinical studies performed in animal models are known to translate poorly to humans and therefore these systems provide unprecedented advantages: human neurons in a controlled environment that have the genetic signature of psychiatric or mental disorders borne by the donor patient, such as Alzheimer’s or Parkinson’s disease. Finally, compared to animal studies where overwhelmingly only male animals are studied, stem cell research can operate on both sexes.The combination of new biomaterials, genome engineering and massively parallel single-cell transcriptomics opens opportunities to precisely study human brain diseaseA new exciting development is the possibility to form so-called assembloids, whereby organoids of different brain regions, as for example cortical and thalamic neural ensembles, are brought in proximity and self-assemble into anatomically correct brain regions. These approaches are necessary to study disorders like epilepsy. However these cultures lack physiological sensory input which are key in the development of mental plasticity. Here we plan to overcome this limitation by integrating new mesh-based electrodes that integrate seamlessly into brain tissue and expand symbiotically with the neurosphere as it grows, and thereby have a spatially refined mean to measure but also elicit neural activity. This will shed light on how electric maturation of these neurospheres comes about and help shape them to an anatomically more faithful brain model.

Оригинален текст от CORDIS (на английски).

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Данни: CORDIS, © Европейски съюз