Suitability of Human Mesenchymal Stem Cells Derived from Fetal Umbilical Cord (Wharton’s Jelly) as an Alternative In Vitro Model for Acute Drug Toxicity Screening

Abstract

Preclinical toxicity screening is the first and most crucial test that assesses the safety of new candidate drugs before their consideration for further evaluation in clinical trials. In vitro drug screening using stem cells has lately arisen as a promising alternative to the “gold standard” of animal testing, but their suitability and performance characteristics in toxicological studies have so far not been comprehensively investigated. In this study, we focused on the evaluation of human mesenchymal stem cells isolated from the matrix (Wharton’s jelly) of fetal umbilical cord (WJSCs), which bear enhanced in vitro applicability due to their unique biological characteristics. In order to determine their suitability for drug-related cytotoxicity assessment, we adopted a high-throughput methodology that evaluated their sensitivity to a selected panel of chemicals in different culture environments. Cytotoxicity was measured within 48 h by means of MTS and/or NRU viability assays, and was compared directly (in vitro) or indirectly (in silico) to adult human mesenchymal stem cells and to reference cell lines of human and murine origin. Our data clearly suggest that human WJSCs can serve as a robust in vitro alternative for acute drug toxicity screening by uniquely combining rapid and versatile assay setup with high-throughput analysis, good representation of human toxicology, high reproducibility, and low cost.

Cytotoxic Activity of Herbal Medicines as Assessed in Vitro: A Review

“…Cell‐based assays are commonly used as platforms for evaluating cell viability, proliferation and cytotoxicity [69] . Various assessment methods have been used to measure viability or toxicity, and identifying the most appropriate cell health assay method can be a challenging task [70,71] . Therefore, in an attempt to improve the study quality and efficacy, choice of a suitable assay method for cytotoxicity assessment significantly contributes to determining the efficacy of a natural compound [72–74] .…”

“…[69] Various assessment methods have been used to measure viability or toxicity, and identifying the most appropriate cell health assay method can be a challenging task. [70,71] Therefore, in an attempt to improve the study quality and efficacy, choice of a suitable assay method for cytotoxicity assessment significantly contributes to determining the efficacy of a natural compound. [72 -74] Different measurable parameters which are based on the determination of the total protein content, cell number or growth, reduction of vital dye, specific enzymatic release, vital dye release and other measurable parameters, which may be quantified as an indicator for cytotoxicity.…”

miRNA-Guided Regulation of Mesenchymal Stem Cells Derived from the Umbilical Cord: Paving the Way for Stem-Cell Based Regeneration and Therapy

“…Human UCMSCs, as well as their secreted exosomes and other extracellular vesicles, which often carry specific miRNAs involved in key cellular functions, appear to possess significant regenerative, anti-inflammatory, protective, and in some cases, even tumor-suppressing capabilities [62]. Their ameliorative properties, along with their strong self-renewal rate, low immunogenic potential, and non-invasive isolation does indeed make UC-derived MSCs one of the most appealing candidate sources for novel stem-cell-based therapies as well as other applications, including general and tissue-specific toxicity screening [63]. Promising applications of UCMSCs in the context of miRNAdirected regenerative/healing and therapeutic potential are presented in Tables 2 and 3 and in the corresponding Figures 2 and 3, respectively.…”

Stable Chinese Hamster Ovary Suspension Cell Lines Harboring Recombinant Human Cytochrome P450 Oxidoreductase and Human Cytochrome P450 Monooxygenases as Platform for In Vitro Biotransformation Studies

“…For the development of new drug candidates, knowledge about their pharmacokinetics, toxicology, as well as their liver metabolites, are of great importance. Preclinical drug screening requires reliable in vitro cell and/or microsomal systems characterized, e.g., by highly specific phase-1 biotransformation properties to identify main and possible side metabolisation pathways at an early stage [4,5,13]. Of interest is also the in vitro generation of therapeutically active drug metabolites that could substitute prodrug administration and thus bypass the liver first-pass effect.…”