Organoid factory: The recent role of the human induced pluripotent stem cells (hiPSCs) in precision medicine

Abstract

During the last decades, hiPSC-derived organoids have been extensively studied and used as in vitro models for several applications among which research studies. They can be considered as organ and tissue prototypes, especially for those difficult to obtain. Moreover, several diseases can be accurately modeled and studied. Hence, patient-derived organoids (PDOs) can be used to predict individual drug responses, thus paving the way toward personalized medicine. Lastly, by applying tissue engineering and 3D printing techniques, organoids could be used in the future to replace or regenerate damaged tissue. In this review, we will focus on hiPSC-derived 3D cultures and their ability to model human diseases with an in-depth analysis of gene editing applications, as well as tumor models. Furthermore, we will highlight the state-of-the-art of organoid facilities that around the world offer know-how and services. This is an increasing trend that shed the light on the need of bridging the publicand the private sector. Hence, in the context of drug discovery, Organoid Factories can offer biobanks of validated 3D organoid models that can be used in collaboration with pharmaceutical companies to speed up the drug screening process. Finally, we will discuss the limitations and the future development that will lead hiPSC-derived technology from bench to bedside, toward personalized medicine, such as maturity, organoid interconnections, costs, reproducibility and standardization, and ethics. hiPSC-derived organoid technology is now passing from a proof-of-principle to real applications in the clinic, also thanks to the applicability of techniques, such as CRISPR/Cas9 genome editing system, material engineering for the scaffolds, or microfluidic systems. The benefits will have a crucial role in the advance of both basic biological and translational research, particularly in the pharmacological field and drug development. In fact, in the near future, 3D organoids will guide the clinical decision-making process, having validated patient-specific drug screening platforms. This is particularly important in the context of rare genetic diseases or when testing cancer treatments that could in principle have severe side effects. Therefore, this technology has enabled the advancement of personalized medicine in a way never seen before.

Effects of using collagen and aloe vera grafted fibroin scaffolds on osteogenic differentiation of rat bone marrow mesenchymal stem cells in SBF-enriched cell culture medium

“…Understanding the physiology and pathology of many hard tissue diseases can be gained by examining the mineral composition of hard tissue organoids and how they vary over time. The mineralization process, which the authors discovered, was comparable to genuine bone, and the organoids showed more significant mineralization with time, similar to natural bone [12][13][14]. Furthermore, hydroxyapatite crystals are deposited within a collagen matrix as part of the complicated and dynamic process of bone mineralization [15].…”

An efficient induction method for human spinal lower motor neurons and high-throughput image analysis at the single cell level

“…Because ALS symptoms progress rapidly and daily physical activities become impossible for patients within 1-2 years, rapid establishment of patient-derived iPSCs and drug screening of MNs are essential for precision medicine. Although there are many problems to be solved in the practical application of personalized medicine using iPS cells (Shin et al, 2018, Novelli et al, 2023, Palasantzas et al, 2023, Nguyen et al, 2023, we believe that our method can shorten the time required for drug screening and contribute to practical application.…”

Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease

“…Here, we leveraged gene editing in human keratinocytes and an organotypic epidermal model to elucidate the pathogenic mechanisms underlying a rare genetic disorder, which allowed us to identify much-needed potential therapeutic avenues. Though testing if our findings translate to an effective treatment approach for patients remains to be done, our work nevertheless underscores the power of organoids to generate large-scale transcriptomic and proteomic datasets that can be mined for rational drug targets to validate both in vitro and in patient-derived tissues (77,(79)(80)(81)(82).…”

“…The copyright holder for this preprint this version posted March 7, 2023. ; https://doi.org/10.1101/2023.03.07.531620 doi: bioRxiv preprint proteomic datasets that can be mined for rational drug targets to validate both in vitro and in patient-derived tissues (77,(79)(80)(81)(82).…”