Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs

TLDR

The study presents a functional human 4‑organ system under continuous, serum‑free, pumpless flow conditions for 14 days to evaluate multi‑organ toxicity. The platform employs a pumpless continuous‑flow design, and the integrated cardiac, muscle, neuronal, and liver modules were assessed for pharmacological relevance after a 48‑hour exposure to five drugs with known side effects at day 7. Computer simulations confirmed acceptable flow rates and shear stress, the 14‑day system maintained viability and functional activity across all modules, and drug responses aligned with published toxicity data, demonstrating the model’s ability to recapitulate multi‑organ toxicity and advancing toward a human‑on‑a‑chip assay.

Abstract

Abstract We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems and constitutes a step towards an in vitro “human-on-a-chip” assay for systemic toxicity screening.