H2020Индивидуална стипендия2019–2022

GHSO · Generation of human steroid-producing organoids: a new approach to treat adrenal insufficiency

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

Период: 2019-06-01 → 2022-05-31
Финансиране от ЕС: 246 669 €
Участници: 2
Схема: MSCA-IF-GF

Линиите свързват координатора с партньорите.

Накратко на български

Лабораторно създадени органиоиди от човешки клетки се изследват като алтернатива на хапчетата при недостиг на кортизол. Тези клетки, защитени в специални устройства, биха могли да отделят нужните хормони според нуждите на организма, вместо да се прибягват до ежедневно приемане на лекарства.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Generation of human steroid-producing organoids: a new approach to treat adrenal insufficiency

Adrenal insufficiency is a disorder that occurs when the adrenal glands do not produce enough levels of certain hormones, including cortisol, a hormone essential for life. Current treatments for adrenal insufficiency are based on hormone replacement therapy (HRT), consisting of 2 or 3 daily doses of the missing hormones in a pill format. The general purpose of this proposal is to find alternative treatments for patients suffering from adrenal insufficiency using cells that can produce hormones, generated in the laboratory. The overall significance and importance of this technology is the ability to transplant hormone-producing cells that can be properly regulated by the patient’s body, responding with adequate hormone secretion in a time and dose dependent manner. To avoid rejection of the implanted cells by the immune system, we aim to encapsulate (protect) cells into devices developed for this purpose.

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

Цел на проекта

The adrenal cortex is essential for life; it is the primary site of steroid synthesis, producing glucocorticoids, which affect carbohydrate metabolism and mediate the mammalian stress response and mineralocorticoids, which control blood volume and salt homeostasis. Adrenal insufficiency (AI), which can be life threatening, is cause by a number of adrenal disorders, and lifelong management of these patients with exogenous steroids can be challenging. No drug suitably mimics the diurnal pattern of cortisol noted in healthy individuals, and objective variables to measure hormonal replacement therapy quality are lacking. The ability to generate steroid-producing cells from pluripotent stem cells through cell reprogramming, a process where a specialized cell type is induced to transform into a different cell, offers a new paradigm for functional studies, modelling human disease and drug testing and eventually can be used as a cell source for cellular therapies for patients suffering from adrenal conditions. This proposal aims to develop methodologies to generate adrenal-like organoids from human embryonic stem cells (hESCs), which have not been generated so far, without requiring overexpression of exogenous transcription factors and test them in in vivo models of adrenal insufficiency. Because small molecules provide several distinct advantages in controlling protein functions (e.g., temporally controllable, reversible, tunable and tractable) I will utilize them for a faster, more efficient, and directed cellular reprogramming. CRISPR-Cas9 genome engineered steroid-producing organoids harbouring common mutations found in congenital adrenal hyperplasia (CAH), the most common type of AI, will be generated and used as a disease modelling platform to study CAH. This proposal aims to accelerate the translation of this promising bench research to patients affected by adrenal insufficiency over the next 10 years.

Оригинален текст от CORDIS (на английски).

Участници

TECHNISCHE UNIVERSITAET DRESDEN · DresdenКоординаторГермания
CHILDREN'S HOSPITAL CORPORATION · BostonСъединени щати