H2020Индивидуална стипендия2015–2017

OsteoNano · Spatial nanoscale control of growth and adhesion factors to enhance the osteogenic differentiation of mesenchymal stem cells

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

Период: 2015-05-01 → 2017-04-30
Финансиране от ЕС: 159 461 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Биомиметични платформи с хепаран сулфат се използват, за да се подобри действието на протеина BMP-2 при превръщането на стволови клетки в костна тъкан. Това помага за намаляване на страничните ефекти, като образуването на кост на неправилни места или рак.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Spatial nanoscale control of growth and adhesion factors to enhance the osteogenic differentiation of mesenchymal stem cells

The main challenge of regenerative medicine is to understand the molecular basis of tissue-specific differentiation and then to apply the appropriate chemical and physical cues to guide stem cell fate. In particular, bone tissue engineering is one of the major societal challenges in orthopedics, cranio-maxillo-facial surgery and dentistry, partially due to the aging of the population. OsteoNano project focused on improving the efficiency of a biochemical factor, named bone morphogenetic protein 2 (BMP-2), to drive stem cells osteogenic differentiation. BMP-2 is a growth factor already used in clinics for spine fusion and tibial fractures. However, this practice presents important sides effects such as ectopic bone formation and eventually cancer. The objectives of OsteoNano project are initially to design a 2D cellular support (biomimetic platforms) able to mimic the natural presentation of BMP-2 to cell surface. In vivo, BMP-2 is bound to extracellular matrix (ECM) components, in particular to the glycosaminoglycan heparan sulphate (HS), a sugar ubiquitously present on cellular surface and in the ECM. In normal conditions HS is not soluble but grafted on core-protein. For this reason the biomimetic platforms here developed present HS immobilized and oriented via its reducing end to a Streptavidin monolayer. The second objective is to investigate the molecular interaction between BMP-2 and HS by the characterization of their binding affinity and the kinetics of release of BMP-2 from HS film. Finally stem cells can be plated on these surfaces and cellular mechanism, in particular osteogenic differentiation driven by BMP-2 signalling pathway, analysed. I proved that HS, once immobilized on the biomimetic platforms, enhances the biological effect of BMP-2 promoting osteogenic differentiation of mesenchymal stem cells and inhibiting the effect of noggin, the natural BMP-2 antagonists. As conclusion, the immobilization of HS on 3D scaffold could be a future strategy to improve the effect of BMP-2 for bone repair.

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

Цел на проекта

In OsteoNano project the training-through-research is targeted at the developing of biomimetic surfaces to study and control the osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). Osteogenic differentiation of hMSCs can be guided by growth factors, such as bone morphogenetic protein 2 (BMP-2). Currently, recombinantly expressed BMP-2 is applied clinically to enhance the healing of fractured sites. However, the absence of a control over the growth factor surface density and adhesion of cells induce side effects such as ectopic bone formation. The first aim of this project is to present BMP-2 to hMSCs in a spatially controlled manner by applying surface sensitive and high-resolution techniques. The growth factors will be linked to the surface using glycosamminoglycans (GAGs) such as heparan sulphate (HS), and combined with adhesives molecules such as cyclic RGD sequences, which are known to increase the osteogenic effects of BMP-2 by activation of Integrin alphaV-beta3 and alpha5beta1. Our approach will be to design biomimetic surfaces with stepwise increasing complexity, by binding each component in a controlled manner, in terms of orientation, surface density and spatial arrangement. By using these functionalized substrates for hMSCs osteogenic differentiation we will answer several fundamental questions regarding the role of BMP-2 and its interaction with HS and RGD sequences on the osteogenic commitment of hMSCs. The biomimetic surfaces proposed here, present several fundamental studies, advantages and breakthroughs (i) reduced use of BMP-2 bound on the surface: indeed (i) the binding prevents the cellular internalization of the growth factors; (ii) possibility to enhance the osteogenic differentiation by surface co-presentation of BMPs or/and of RGDs; (iii) surface versatility with respect to stiffness which could positively impact osteogenic differentiation.

Оригинален текст от CORDIS (на английски).

Участници

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENКоординаторГермания