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Accession IconSRP064796

Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy

Organism Icon Mus musculus
Sample Icon 2 Downloadable Samples
Technology Badge IconIllumina HiSeq 2000

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Description
Long-term survival and antitumor immunity of adoptively transferred CD8+ T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (??m). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-??m-sorted CD8+ T cells. Transfer of these low-??m T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-??m cells. Use of ??m-based sorting to enrich for cells with superior metabolic features was observed in CD8+, CD4+ T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer. Overall design: mRNA-Sequencing of gene expression profiles in mouse CD8 cells (TMRM high and TMRM low).
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