TorPause: Efficient Static Organ Preservation for Transplants

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Abstract
Transplantation is limited by how long organs survive outside the body. Current methods slow metabolism or sustain physiological support, but neither eliminates ischemia-reperfusion injury, which shortens storage and drives organ discard. Embryonic diapause and hibernation show that mammalian cells retain a latent capacity for reversible metabolic arrest. Screening the PI3K-mTOR axis, we identified a dual inhibitor that reversibly pauses embryonic stem cells at ambient oxygen and holds mouse embryos in arrest for 8.5 days. Combined with a mitochondria-targeted hydrogen sulfide donor, this yields TorPause, a two-component flush compatible with existing preservation protocols. In a rat liver transplantation model, TorPause reduced structural injury and improved recipient survival after 5 hours of static storage at room temperature, potentially expanding the usable donor pool.
Funding Information
  • Swedish Research Council (2017-0034)
  • Stanford Transplant and Tissue Engineering Center of Excellence fellowship
  • National Science Foundation Graduate Research Fellowship
  • Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University
  • Arnold & Barbarbara Silverman Endowment at the Stanford University School of Medicine
  • Nancy & Richard Robbins Family Foundation
  • California Institute for Regenerative Medicine (DISC2P-11662)
  • Japan Agency for Medical Research and Development (JP22bm1004002)
  • Japan Agency for Medical Research and Development (JP23bm1123041h0001)
  • Ralph and Marian Falk Medical Research Trust

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