Repair/Regenerate via the circulation of mesenchymal stromal cells between organs
From their development to the end of their lives, most organisms experience a gradual decline in their regenerative capacity. Schematically, each organ can be divided up into a functional compartment, the parenchyma, and a stromal compartment, the stroma, which supports the parenchymal cells of the organ. In the stroma, there is a population of cells with multiple differentiation capacities, the mesenchymal stromal cells (MSCs). MSCs exhibit a strong regenerative potential and are considered key players in the regeneration of damaged tissue. Adipose tissue is, to date, the richest reservoir of MSCs where they are called adipose stromal cells or ASCs. Unexpectedly, this ASC reservoir can be mobilized in response to stresses of inflammatory and/or lesional origin. Once released, ASCs infiltrate the damaged/inflamed organ and participate in its remodeling and/or regeneration.
How are ASCs recruited? What are the functional characteristics of mobilized ASCs? How does the contribution of ASCs to regeneration evolve according to age-related frailty ? All these questions remain unanswered.
The STROMAGICS project consists in deciphering the relationship between stromal dynamics and age-related functional decline. Our scientific objectives are the following:
- To identify the molecular and cellular characteristics of mobilizable ASCs and the mechanisms controlling and enabling this original dynamics
To characterize this dynamic in the context of aging
Molecular and cellular mechanisms controlling the dynamics of ASCs in response to distant tissue stress
We are analyzing the heterogeneity of ASCs in terms of motility, differentiation capacity and metabolomic profile.
How do ASCs circulate between organs in response to distant tissue stress?
We are trying to identify the paths used by ASCs to circulate and the molecular and cellular mechanisms they use to navigate between organs. In particular the blood pathway and fascia. We are also exploring the control of these dynamics exerted by the nervous system.
Functional decline and analysis of ASC dynamics
In this part of the STROMAGICS project, we investigate whether functional decline is associated with altered inter-organ dialogue in response to tissue damage in animal models and human.
Cécile Dromard Berthezene
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