Abstract
Ex vivo cell/tissue-based models are an essential step in the workflow of pathophysiology studies, assay development, disease modeling, drug discovery, and development of personalized therapeutic strategies. For these purposes, both scientific and pharmaceutical research have adopted ex vivo stem cell models because of their better predictive power. As matter of a fact, the advancing in isolation and in vitro expansion protocols for culturing autologous human stem cells, and the standardization of methods for generating patient-derived induced pluripotent stem cells has made feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Furthermore, the potential of stem cells on generating more complex systems, such as scaffold-cell models, organoids, or organ-on-a-chip, allowed to overcome the limitations of the two-dimensional culture systems as well as to better mimic tissues structures and functions. Finally, the advent of genome-editing/gene therapy technologies had a great impact on the generation of more proficient stem cell-disease models and on establishing an effective therapeutic treatment. In this review, we discuss important breakthroughs of stem cell-based models highlighting current directions, advantages, and limitations and point out the need to combine experimental biology with computational tools able to describe complex biological systems and deliver results or predictions in the context of personalized medicine.
Highlights
Over the past decades, much of our understanding of human physiology and pathologies has been derived from studies on animal models
The main criticisms about the actual predictive value of animal models are related to (i) their limits on fully recapitulating the human physiology/pathologies, (ii) their maintenance costs, and (iii) the ethical issues associated with their use [2,3,4]
Tissue engineering applies the concepts of engineering and biology to develop scaffold-based systems with the aim of reproducing the structure and the physiological functions of healthy tissues
Summary
Much of our understanding of human physiology and pathologies has been derived from studies on animal models. The main criticisms about the actual predictive value of animal models are related to (i) their limits on fully recapitulating the human physiology/pathologies (e.g., different pharmacokinetics and toxicokinetic; presence of alternative pathways that may interfere with the progression of a given disease; different immune-response),. Even if animal models, especially mammals, are still an essential tool before a novel therapeutic strategy enters clinical trials, their use is severely restricted [5]. In order to overcome these limitations, scientists have focused on finding alternative approaches and tools that could recapitulate the homeostasis of. Med. 2020, 10, 8 cells/tissues as well as pathological alterations. In vitro cell/tissue models today became a very promising tool for investigating human development, physiology and disease pathogenesis. We review the progress made in establishing the most proficient cell/tissue modeling, from basic cell culture systems to more innovative organoid platforms
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