H2020Индивидуална стипендия2022–2024

NeurTransHet · Investigating human neuronal transplantation integration and interaction at the single cell level

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

Период: 2022-01-01 → 2024-12-06
Финансиране от ЕС: 162 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Трансплантираните неврони се изследват на ниво единична клетка, за да се разбере как се свързват с тъканите при мозъчни наранявания или болест на Алцхаймер. Това помага за по-доброто разбиране на възстановяването на мозъка и подобряването на бъдещи терапевтични методи.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Investigating human neuronal transplantation integration and interaction at the single cell level

Neuronal loss is a hallmark of various brain disorders, such as Alzheimer’s disease, and injuries, like traumatic brain injury. However, the brain's ability to replace lost neurons from its own neural stem cells is highly limited and restricted to specific regions. One promising strategy to restore function is the transplantation of exogenous neuronal cells directly into the affected areas. While previous studies have focused on the connectivity of transplanted neurons (tNs), little is known about the diversity within the transplanted cell population and how the local brain environment influences their integration. This project aimed to provide a clinically relevant understanding of how tNs integrate into the injured brain. By characterizing the heterogeneity of tNs, we specifically examined the diversity of their synaptic interactions within the host tissue. Furthermore, we investigated the role of the local environment in shaping tN integration. Notably, we identified an upregulation of the immune receptor Trem2 at the transplantation site. When TREM2 was removed from the environment, we observed altered connectivity between tNs and the host neural network. These findings contribute to a deeper understanding of neuronal transplantation and may help refine future therapeutic approaches for brain repair.

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

Цел на проекта

NeurTransHet will shed light on the heterogeneity of neuronal transplantations and the relationship with their environment. The aim of this project is to bring neuronal transplantation closer to clinical implementation by understanding the intricacies of individual transplanted cell contribution, and later applying this knowledge to engineer them. Neuronal loss underlies various brain disorders, such as Alzheimer’s disease, and injuries, such as traumatic brain injuries, resulting in life-long impairment. For example, dementia, a widespread (a new case every 3 seconds worldwide) condition stemming from neuronal loss, has devastating effects on the patients, their families and their communities. Thus, approaches aiming at replacing the lost neurons by transplantation are not only attractive from a health perspective, but also from a socio-economic standpoint. Many studies have explored neuronal transplantation, albeit with varying degrees of success. This is due to a lack in our understanding of how transplants integrate and interact with their host environment. Additionally, several studies gave evidence that transplanted cells are a heterogenous population, however, so far this heterogeneity has not been addressed in terms of function on integration and interaction. The recent advent of single cell transcriptomic technology, coupled with imaging techniques providing high-resolution spatial information, makes it possible to go beyond global interaction and closely dissect the individual neuronal transplants and their environment. Moreover, the possibility of transplanting cells of human origin in mice increases the clinical relevance of the results. During this two-year fellowship under the supervision of Prof. Dr. Magdalena Götz, who is a world-renowned scientist in neuronal cell replacement methodologies, I will transition into an independent research group leader investigating the role of cell heterogeneity in disease.

Оригинален текст от CORDIS (на английски).

Участници

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggКоординаторГермания