Antisense Oligonucleotides against Let-7 Enhance the Therapeutic Potential of Mesenchymal Stromal Cells.

ABSTRACT: Let-7 miRNAs have pleiotropic cellular functions in cell proliferation, migration, and regenerative processes. Here, we investigate whether the inhibition of let-7 miRNAs with antisense oligonucleotides (ASOs) can be a transient and safe strategy enhancing the therapeutic potential of mesenchymal stromal cells (MSCs) to overcome their limitations in cell therapeutic trials. We first identified major subfamilies of let-7 miRNAs preferentially expressed in MSCs, and efficient ASO combinations against these selected subfamilies that mimic the effects of LIN28 activation. When let-7 miRNAs were inhibited with an ASO combination (anti-let7-ASOs), MSCs exhibited higher proliferation with delayed senescence during the passaging into a culture. They also exhibited increased migration and enhanced

SUBMITTER: Lee DW 

PROVIDER: S-EPMC10218563 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature