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FLAMES

Agnès Coste

FLAMES : INFLAMMAGING CONTROL BY DYNAMIC MSC / MYELOID CELL CROSSTALK

Team Flame

The objective of the FLAMES team is to integrate stromal dynamics, inflammation and metabolism in the understanding of the loss of biological functions during aging to maintain and/or restore functional capacities. Our project aims to demonstrate that age-related chronic inflammation results from a defect of resolution of inflammation in tissues due to altered dialogue between macrophages and mesenchymal stromal cells (MSC).

This project is based on the use of innovative animal models, in vitro 4D strategies to reproduce tissue heterogeneity, as well as in silico approaches to study the inflammatory response and their effects on tissue repair.

The goal of our research project is to contribute to the identification of potential therapeutic targets to restore the dialogue between MSCs and macrophages to promote the development of a pro-resolutive response.

 

research axis

AXIS 1

Mapping of Macrophages and MSC heterogeneity during physiological and pathophysiological aging

Our group are looking at the modification of the phenotype and of the modification of the functional capacities of macrophages and MSC during aging in human and in mice. This will be done by using confocal microscopy, flow cytometry and single cell transcriptomic approaches, as well as functional assays. In addition, as the macrophages heterogeneity relies also on their origin, the modification of the macrophage origin during aging are studying using lineage tracing and animal models of hematopoietic reconstruction.

AXIS 2

Identify cellular and molecular targets that control the MSC/ Macrophages crosstalk during aging

Our group is characterizing  the receptors and soluble factors involved in the interaction between MSC and macrophages and how this MSC-macrophage communication is modified during aging. We currently focus on CD54 as a key molecule in the cross-talk between Macrophages and MSCs (Esapgnolle et al) and on ecosanoids that play a central role in resolution of inflammation (ref).

Cellules
Interaction entre les cellules stromales mesenchymateuses (vert) et les macrophages (violet) via le CD54 (jaune) in vitro (image de gauche) et in vivo (image de droite). Crédit: A.Varin-C.Barreau
Interaction between mesenchymal stromal cells (green) and macrophages (purple) through CD54 (yellow) in vitro (left) and in adipose tissue (right). Photo credit: A.Varin-C.Barreau

The targets involved in MSC-macrophage interaction are studying using murine and human experimental models of vascularized 3D culture systems that combine different cellular actors

  • endothelial cells
  • immune cells
  • stroma
Communication between multiple spheroids generated from MSC after 8 days in a hydrogel »
Scanning electron microscopy image of a self-organized MSC network in a biomaterial pore after 15 days of culture in a perfused bioreactor

AXIS 3

Strategies to restore the pro-resolutive macrophages through the re-education of macrophages or MSC/ Macrophages crosstalk

Our group is also developing different therapeutic approaches to reduce “inflammaging”.  Pharmacological, nutritional approaches and also cell therapy  approaches will be developed.

This research is carried out in collaboration with university partners and private companies.

team members

Agnès Coste 2

Agnès Coste

Group leader PU-UT3 Pharmacy
Lise Lefévre

Lise Lefèvre

MCU-UT3 Pharmacy

Macrophage polarization, infection and immunity, nuclear receptor, inflammation and its resolution

Hélène Authier

Hélène Authier

MCU-UT3 Pharmacy

Innate immunity/macrophages; mesenchymal stromal cells, cell-cell interaction, cell therapy, inflammation

Audrey Varin

Audrey Varin

CR-EFS

Mesenchymal stromal cells, organoids, Biomaterials, 3D modelisation, stroma

Nicolas Espagnolle

Nicolas Espagnolle

CR-EFS

Inflammaging, SASP, mesenchymal stromal cell and macrophage cross-talk, senescence

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Victorine Douin-Echinard

MCU-UT3 Pharmacy

Cellules stromales mésenchymateuses, ingenierie cellulaire et tissulaire, organoides, bioréacteurs, culture 3D

Mélanie_Gadelorge

Mélanie Gadelorge

Engineer-EFS
Benedicte Bertrand2

Benedicte Bertrand

Technician-UT3 Pharmacy
Jean-Gérard Descamps 2

Jean-Gérard Descamps

Technician-EFS
Mathilde L

Mathilde Lavernhe

Engineer-UT3 Pharmacy

Myelome, 3D models

Caroline

Caroline Siekaniec

Technician-EFS
Ali

Ali Sanouj

PhD student
Mathilde R

Mathilde Romano

PhD student

Macrophages, wound healing, collagen, resolution of inflammation, immunity

Marie Salon 2

Marie Salon

PhD student

Macrophages, hématopoïèse, régénération, vieillissement et tissu adipeux 

Adèle Arlat2

Adéle Arlat

ATER
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Judith Fillaux

MCU-PH-UT3 Medicine
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Sophie Cassaing

MCU-PH-UT3 Medicine
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Marianne Dutour

Technicienne
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Laurent Alric

PU-PH-UT3 Medicine
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Bernard Pipy

DR émérite Inserm
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Brigitte Sallerin

PU-PH

Publications

Team Partners

scientific partners
financial supports