Speaker: Prof. Dr. Thomas Skutella

 

Talk Title: Rejuvenated MSC-derived extracellular vesicles from aged donors show enhanced potency in macrophage immunomodulation and wound healing

 

Affiliation: Head of the Department of Neuroanatomy in the Institute for Anatomy and Cell Biology, Heidelberg University, Germany.

 

Abstract: 

Mesenchymal stromal cells (MSCs) from aging donors lose regenerative and immunomodulatory potency, and there are no validated measures to distinguish rejuvenated from residual senescence. We reprogrammed bone-marrow MSCs from four adult donors to induced pluripotent stem cells and re-differentiated them under two conditions. iMSCs clustered with MSCs, showed promoter methylation inversely coupled to gene expression, retained residual senescence and desmosome signatures, and their EVs suppressed LPS-induced IL-6 and TNF-α, outperforming EVs from aged MSCs and hiPSCs. iMSC-EVs also promoted endothelial wound closure and gained a distinct protein- and small-RNA cargo signature, including NF-κB-targeting miRNAs and reproducibly reduced piRNAs. The same potency and rejuvenation framework was assessed in vivo in a diabetic wound model. These quality and potency metrics may support release testing and mechanism-guided product development of rejuvenated MSC-derived therapeutics.