Method Profile

Paired Alteplase Evaluation with Ex Vivo Human Lung Digital Twins

Baseline data from an isolated human lung generate an untreated forecast for comparison with its measured response to alteplase.

LungComputational Models
A scanning electron micrograph showing the thin walls and open spaces of human lung alveoli.
Scanning electron micrograph of human lung alveolar structures. (David Gregory & Debbie Marshall, CC BY 4.0)

Research Applications

Evaluate short-term organ-specific drug effects with a computational paired reference, alongside conventional controls.

Model & Design

Hybrid physiological and machine-learning forecasts trained on human EVLP data, coupled to real perfused donor lungs.

Experimental Format

A first-hour baseline predicts second- and third-hour untreated values; compare the physical lung after 20 mg alteplase with that forecast and with a historical untreated cohort.

Model Components

  • Component

    Development and test evidence

    Description

    951 documented EVLP cases from a 1,000-case review; modality-specific complete-case samples; 45 separate clinical test cases from the same center; alteplase-treated cases excluded from training.

  • Component

    Drug experiment

    Description

    16 alteplase-treated lungs, 2 excluded for insufficient perfusion follow-up; 6 suitable and 8 unsuitable lungs analyzed.

Measurements & Endpoints

  • Pulmonary arterial pressure
  • Short-term edema measure
  • Physiological/biochemical/image forecast error

Analysis

Keep clinical test, simulated illustrative and drug-treated cohorts separate. The paired untreated trajectory is predicted, so the drug contrast depends on forecast calibration.

Published Evidence

  • Study Design

    Independent same-center forecast test and real-world treatment-use comparison, with suitable and unsuitable subgroups analyzed separately.

    Study Sample

    45 clinical test lungs; 50 simulated illustrative profiles; 14 analyzed treated lungs (6 suitable, 8 unsuitable) after 2 of 16 exclusions.

    Comparison

    Each treated lung’s untreated digital forecast; randomly selected historical untreated group of 6 lungs.

    Finding

    Suitable six: conventional comparisons were nonsignificant, while paired PAP at 2 hours was lower (P = 0.031). Edema was not significantly different (P = 0.063). Unsuitable eight did not show the same pressure-lowering response.

    Interpretation & Limits
    • First-three-hour, transplantation-related measurements bound the use.
    • Independent test remains at the originating center; external validation is needed.
    • An edema endpoint does not establish whole-body or comprehensive drug safety.

Sources

  1. Digital twins of ex vivo human lungs enable accurate and personalized evaluation of therapeutic efficacy. Nature Biotechnology. Published 4 May 2026. doi:10.1038/s41587-026-03121-4 ↗