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Abstract

Biomedical research is essential for the discovery of new medications and treatments, and is built upon the cooperation of preclinical (in vitro/vivo) research and clinical trials. However, 85% of treatments previously successful in vitro/vivo fail in clinical trials, suggesting that in vitro models are poor indicators of clinical success. The issue lies in conventional “two-dimensional” in vitro models containing genetically identical cells grown on a flat plate, which lack the variety of cell types and cooperation/structure found in real tissue. Moreover, 2D in vitro models do not simulate humans’ genotypic variability, which affects both pathophysiology and treatment effectiveness. 3D in vitro disease models (e.g. organoids/spheroids) include the extracellular components, structures, cell-cell interactions, and microenvironment observed in human tissue, resulting in more physiologically accurate disease models. This paper consolidates current research of 3D models of varying complexities for different diseases to propose an effective and efficient solution for creating 3D in vitro models. Organoids should be the model of interest for organ/tissue-specific diseases and tumors, while patient-derived xenografts formed by implanting organoids into humanized mouse models are useful for studying body-wide disease/treatment effects. Growing organoids in prepared hydrogels allows them to mimic a human extracellular matrix and microenvironment, and adjusting the hydrogel’s characteristics allows control over organoid growth/differentiation. Sourcing undifferentiated stem cells from patients of different ethnicities, ages, and socioeconomic statuses allows representation of diverse populations and corresponding epigenetics. Adipose stem cells are abundant in humans and easily accessible with minimally invasive procedures.

Publication Date

2023

Keywords

Biomedical research, in vitro, in vivo, clinical trials, disease model, genetic diversity, organoids, drug efficacy

Current Academic Year

Freshman

Faculty Advisor/Mentor

Joshua Barton

Rights

© The Author(s)

A Three-Dimensional in vitro Model of Disease That Improves Preclinical Research by Incorporating Genetic Diversity and Increasing Physiological Accuracy

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