TISSUE ENGINEERING & EXTRACELLULAR VESICLES APPLIED TO RHEUMATIC DISEASES

Group leader

Danièle NOEL

Research Director Inserm (DR1)

Contact information:
Phone : +33 4 67 33 04 73
e-mail: daniele.noel[a]inserm.fr

Co-leader

Marie Morille

Associate Professor (Montpellier University, Pharmacy School)

Contact information:
Phone : +33 4 67 33 04 80
e-mail: marie.morille[a]umontpellier.fr

Keywords:

Extracellular vesicles (EV)

Mesenchymal stromal cells (MSC)

Cartilage

Osteo-articular and autoimmune diseases

Biotherapies

Regeneration

3D bioprinting

EV engineering 

Targeted nanomedicine

PEG alternatives

The group members:

GROULT Emeline (CRCN)

MARIA Alexandre (MCU PH)

THERON Alexandre (AHU)

ROZIER Pauline (ASH)

ABEZA Claire (IR)

BONY Claire (IR)

MAUMUS Marie (IR)

SERVANT Zoé (IR)

DAURAT Morgane (IE)

GIAMBERINI Maxime (IE)

GILLES Alexia (AI)

VESSIERE Anaïs (AI)

MILLA Vanessa (Post-doc)

ROCHA Eliza (Post-doc)

SICOT Marion (Post-doc)

DUPUY Silouane (PhD student)

GUTH Lucien (PhD Student)

IBARISSEN Dalia (PhD Student)

IBN-ELFEKIH Zeineb (PhD Student)

GRAVERON Guilhem (PhD Student)

ROBERTS Lauren (PhD Student) 

SOTO‐ARAYA Anais (PhD Student)

We develop innovative therapeutic approaches based on the use of natural nanoparticles, extracellular vesicles derived from mesenchymal stromal cells, and synthetic nanoparticles (lipid and polymeric). Our multidisciplinary approach aims to optimize these nanosystems for targeted clinical applications.

Our team gather scientists, physicians, and teacher-researchers, draws on complementary and highly integrated expertise covering fundamental biology, engineering, nanomedicine, biotherapies, and clinical research. This multidisciplinary approach, which is rare in the French ecosystem, allows us to address the issues of regenerative medicine and immunotherapy in a comprehensive manner.

Our main lines of research:

Our research program is structured around four complementary areas :

1. Understanding and exploiting the therapeutic potential of mesenchymal stromal cells and their secretome:

We are studying the biological mechanisms of extracellular vesicles derived from mesenchymal stromal cells in order to optimize their therapeutic potential for the treatment of autoimmune and osteoarticular diseases, including osteoarthritis, systemic scleroderma, and rheumatoid arthritis.

2. Modifying extracellular vesicles to optimize their therapeutic functions

We are developing rational engineering strategies, seeking to establish an optimal balance between functional modification and preservation of the intrinsic biological properties of these natural nanovectors. Breaking with conventional approaches focused on loading the lumen of extracellular vesicles, we are developing innovative approaches that exploit their surface as a therapeutic or targeting platform, with a specific focus on engineering efficiency quantification.

3. “PEG-free” nanomedicines and surface modification

We develop original nanomedicines designed to modulate immune responses, focusing primarily on the surface modification of lipid nanoparticles. We explore alternatives to PEG, such as poly(oxazolines), in order to design formulations that can be (re)administered intravenously. Our team is particularly involved in the activities of the Immun4cure IHU to develop rational and reproducible targeting methods to create systems for in vivo reprogramming of immune cells in order to restore homeostasis in autoimmune diseases.

Finally, the detailed characterization of surface modifications, both for extracellular vesicles and synthetic nanovectors, is a major cross-disciplinary focus of our activity, relying on cutting-edge technological platforms (EVe and RNA clinic platforms) with state-of-the-art equipment (FFF-MALS).

4. Development of cartilage engineering approaches

We aim at better understanding osteo-articular diseases using relevant in vitro models based on organoid formation and 3D bioprinting approaches. This should allow to develop innovative therapeutic strategies for cartilage repair to restore joint function. Organoids and joint-on-chip technologies should feature a complex joint environment to get the proper structural organization required for both cartilage and sub-chondral bone formation. The optimized combinations of biomaterials, cells, bioactive factors are tested in vitro and in vivo to evaluate the potential of cartilage and bone formation by mesenchymal stromal cells for tissue engineering applications. New-generation biomaterials are generated in collaboration with chemists and close interactions with biomecanicians for biomechanical stimulation and characterization of neotissues. Joint-on-chips and organoids will be used to develop models mimicking the inflammatory or degenerative context of rheumatic diseases and evaluate cellular or pharmalogical treatments.

Bibliographical references