Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs
نویسندگان
چکیده
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.
منابع مشابه
In vitro evaluation of human xenobiotic toxicity: scientific concepts and the novel integrated discrete multiple cell co-culture (IdMOC) technology.
In vitro human-based experimental systems represent a relevant preclinical tool for the definition of human xenobiotic properties as human-specific xenobiotic properties, by definition, cannot be detected with nonhuman laboratory animals. For the evaluation of human-specific xenobiotic toxicity, the experimental system should have human xenobiotic metabolism as well as cell populations represen...
متن کاملI-5: Multicellular Human Testicular Organoid: A Novel 3D In Vitro Germ Cell and Testicular Toxicity Model
Background Background: Mammalian spermatogenesis is regulated through paracrine and endocrine activity, specific cell signaling, and local control mechanisms. These highly specific signaling interactions are effectively absent upon placing testicular cells into two-dimensional primary culture. The specific changes that occur between key cell types and involved spermatogenesis signaling pathways...
متن کاملRevolutionizing Tissue Engineering through Mirroring Cell Niche and Application of Natural Compounds
onsidering the high prevalence of severe organ failures due to the cancer, congenital anomaly, or trauma, and the consequent needs for tissue transplantation, deficiencies in tissues and organs are a huge challenge for regenerative medicine at the moment. More than 40 years have passed since the term ‘tissue engineering’ was created as a new th...
متن کاملMultiple Organ Damage Due to Boric Acid Toxicity
Background: Boric acid (BA) is commonly used as pesticide, disinfectant and wood preservative. Its ingestion can cause serious organ damages resulting in death. Case report: A 19 year old man was found dead with two empty packs of BA tablets in vicinity of his body. On autopsy examination, brownish stains along with right angle of mouth and right nostril were found. Stomach was damaged with hem...
متن کامل13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.
In the past decade in vitro tests have been developed that represent a range of anatomic structure from perfused whole organs to subcellular fractions. To assess the use of in vitro tests for toxicity testing, we describe and evaluate the current status of organotypic cultures for the major target organs of toxic agents. This includes liver, kidney, neural tissue, the hematopoietic system, the ...
متن کامل