Details

Autor(en) / Beteiligte

• Sukumar, Madhusudhanan
• Liu, Jie
• Mehta, Gautam U.
• Patel, Shashank J.
• Roychoudhuri, Rahul
• Crompton, Joseph G.
• Klebanoff, Christopher A.
• Ji, Yun
• Li, Peng
• Yu, Zhiya
• Whitehill, Greg D.
• Clever, David
• Eil, Robert L.
• Palmer, Douglas C.
• Mitra, Suman
• Rao, Mahadev
• Keyvanfar, Keyvan
• Schrump, David S.
• Wang, Ena
• Marincola, Francesco M.
• Gattinoni, Luca
• Leonard, Warren J.
• Muranski, Pawel
• Finkel, Toren
• Restifo, Nicholas P.

Titel

Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy

Ist Teil von

• Cell metabolism, 2016-01, Vol.23 (1), p.63-76

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •ΔΨm-based sorting segregates short-lived effector from memory T cell precursors•Low-ΔΨm CD8+ T cells demonstrate decreased oxidative stress•Low-ΔΨm T cells demonstrate superior antitumor activity•Low-ΔΨm marks self-renewing hematopoietic stem cells Metabolic fitness is required for long-term function of T cells and HSC. Sukumar et al. describe a simple and clinically feasible method to isolate such metabolically robust cells, using a single parameter—mitochondrial membrane potential (ΔΨm)—for long-term survival, antitumor immunity, and hematopoietic reconstitution.