Blood platelets play a vital role in stopping bleeding. Patients on chemotherapy, polytrauma or platelet abnormalities require platelet transfusions. Currently it is still necessary to understand how platelets are produced in vivo in order to improve the production of platelets in vitro, a major issue of the coming decades.

Platelets are produced by megakaryocytes within the bone marrow, a complex medium that combines cells and extracellular matrix. Bone marrow is a soft, highly dynamic tissue with an uninterrupted flow of cells that migrate to the sinusoidal vessels to migrate into the bloodstream. Our recent observations in 3D culture have shown a positive impact of the rigidity of the culture medium in the morphological maturation of cells and their ability to form platelets.

The objective of this Master 2 project will be to determine which mechanotransduction is responsible for the increase in megakaryocyte maturation and in particular the possible impact of the interaction with the extracellular matrix proteins.
We will study i) the impact of 3D culture in hydrogels of known rigidity, functionalized or not covalently with proteins of the matrix. Such gels are commercially available; ii) the in vivo importance of adhesion to extracellular matrix in the stroma or sinusoidal vessels, using mouse models whose megakaryocytes lack integrins, the main protein receptors in the matrix. These mice are available in the laboratory.

Microenvironment and platelet formation: mechanobiological aspects myelosuppressor

Technologies acquired at the end of the M2 internship:

  • Murine hematopoietic stem cell culture;
  • Immunofluorescence on cells and tissues and observation by confocal microscopy

Manager : Christian Gachet

Team «Biology of thrombopoiesis» – François Lanza

Internship manager : Catherine Leon (CR1 INSERM)

Candidate recruited in the specialty:

Master Physiopathology: From Molecule to Man – Master BMCI