Pericytes (PC) are perivascular cells known to present mesenchymal stem cells (MSCs) like-properties that contribute to tissue regeneration during injuries and diseases. Our team has recently demonstrated that glioblastoma (GB) induces an aberrant up-regulation of chaperone-mediated autophagy (CMA) in PC that modulates their immune function and some MSCs-like properties to support tumor growth. CMA ablation in PC make them useful as anti-tumor treatment. To better understand the PC biology dependent on CMA that let us to characterize the role of CMA in the MSCs-like function of PC, and therefore to determine if CMA in PC might also be a useful target for brain tissue remodeling therapy, we analyzed the MSCs-like properties in CMA-deficient PC compared to controls.

Bioinformatic analyses from RNA-seq studies were related to stemness genes and validated by qPCR. To analyze PC pluripotent properties, we characterized the cell lineage and cell differentiation assays were done using MSCs and adding secretome from WT PC or KO PC (PC from brain of LAMP-2A KO mice). To analyze if CMA in PC was modulated in response to damaged/repaired tissue, LAMP-2A expression was measured in host PC of the damaged areas of a demyelinating mouse model and related to the tissue reparation after intravenous therapy with donor fat or brain PC.

We have found that CMA-deficient PC lose their pluripotent properties and their secretome does not seem to affect the stemness of MSCs compared to PC with CMA. In our mouse model, CMA in host PC seem to be modulated in response to tissue inflammation/injury and repair by cell therapy with donor PC.

CMA seems to be required to maintain the MSCs like-function of PC that contributes to tissue reparation.