Rejuvenation of mesenchymal stem cells by human peripheral blood lymphocytes: A dual-mechanism for targeting senescent cell clearance and promoting cell proliferation in a coculture system [RNA-Seq PBL]

Here we presented a novel approach to combat cellular senescence and promote cell proliferation by coculturing human MSCs with human peripheral blood lymphocytes (PBLs). In a heterogeneous population of MSCs comprising both aged and nonaged cells, PBL effector cells, rather than their cytokines, exhibited a dual role. They selectively induced apoptosis in aged cells by facilitating p53 SUMOylation and activating the p53-dependent mitochondrial pathway, while simultaneously safeguarding younger cells against senescence and promoting cell proliferation by activating Serpinb2/NF-κB signaling. This resulted in a decrease in aged MSCs and an enrichment of rejuvenated MSCs. This process effectively reversed the senescence phenotype, leading to the remodeling of stemness characteristics and the enhancement of functionality within the MSC population. Furthermore, MSCs rejuvenated by PBLs presented an enhanced therapeutic efficacy and a favorable safety profile. The transcriptome changes of PBLs after hAMSCs treatment were determined by RNA-seq analysis. Sequencing was performed on three independent replicates in the PBL group and the ac_PBL group.