[PDF][PDF] Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy

M Sukumar, J Liu, GU Mehta, SJ Patel… - Cell metabolism, 2016 - cell.com
M Sukumar, J Liu, GU Mehta, SJ Patel, R Roychoudhuri, JG Crompton, CA Klebanoff, Y Ji…
Cell metabolism, 2016cell.com
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 (ΔΨm). Comprehensive metabolomic
and gene expression profiling demonstrated global features of improved metabolic fitness in …
Summary
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 (ΔΨm). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-ΔΨm-sorted CD8+ T cells. Transfer of these low-ΔΨm T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-ΔΨm cells. Use of ΔΨm-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.
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