H2020Индивидуална стипендия2016–2018

NVHSC · Neurovascular interplay in the hematopoietic stem cell niches in homeostasis and myeloproliferative neoplasias

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

Период: 2016-04-01 → 2018-03-31
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействието между нервната система и кръвоносните съдове в костния мозък определя поведението на стволовите клетки при стареене и левкемия. Разбирането на тези процеси помага за разработването на нови стратегии за лечение на кръвни заболявания.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Neurovascular interplay in the hematopoietic stem cell niches in homeostasis and myeloproliferative neoplasias

Haematopoietic stem cells (HSC) reside within the bone marrow stem cell niche, which contains different niche cells including, mesenchymal stem cells, endothelial cells as well as neural fibres. In particular, different vascular beds in the bone marrow have been described to control different functions of HSCs. Similarly, different neural fibres have been found in distinct regions of the bone marrow. Interestingly, neurovascular beds particularly differ in regions close to the bone surface (endosteal) in contrast to central bone marrow (non-endosteal). Thus, aim of the project was to study the role of different vascular niches with particular focus on the interaction with the nervous system during steady state, physiological ageing,myeloproliferative neoplasms (MPN) and lekaemia. In line with the demographic change in Europe, age-related haematological complications will increase and early design of novel treatment strategies will be important for minimising age-related complications. Moreover, MPN treatments are currently primarily symptomatic to prevent thrombo-hemorrhagic complications and do not reduce the risk of leukemic transformation and development of secondary myelofibrosis, which can lead to bone marrow failure. Along these lines, relapse from chemotherapy due to mechanisms of chemoprotection is still a mayor complication in leukaemia therapy. Thus, understanding the differential remodelling of the bone marrow microenvironment in MPN and leukaemia progression will contribute to the development of novel niche-targeting strategies and might improve the health of the European society. Moreover, basic research might eventually translate into clinical application and set the stage for European pharmaceutical companies to develop innovative drugs.

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

Цел на проекта

Research of the bone marrow (BM) hematopoietic stem cell (HSC) niche has long been the study of mesenchymal cell populations. Only recently, distinct vascular niches have been identified to balance HSC activation and quiescence. Whereas arterioles together with sympathetic nerves and NG2+Nesbright cells form a niche for quiescent HSC, actively proliferating HSC are closely located to sinusoidal vessels and LepR+Neslow cells. However, it is still elusive how different blood vessels interact with different niche cells in distinct vascular niches during BM homeostasis and leukemic progression. Therefore, the present proposal aims at studying the role of distinct vascular BM niches in controlling HSC maintenance and malignant progression by means of genetic mouse models, FACS analysis, high resolution whole mount BM imaging and RNA sequencing. Besides investigating the direct influence of EC on HSC in different vascular niches, the interaction of EC with perivascular MSC and particularly neurons will be compared between the sinusoidal and arteriolar niche under steady-state and malignant conditions. Changes of the vasculature and downstream effects on HSC and other niche cells will be analyzed during therapeutic targeting of leukemia and the vascular compartment will be evaluated as novel target for niche-targeting leukemia combination therapies.

Оригинален текст от CORDIS (на английски).

Участници

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство