iPSC-Derived Organoids as Therapeutic Models in Regenerative Medicine and Oncology

Abstract

Progress made during the last decade in stem cell biology allows currently an unprecedented potential to translate these advances into the clinical applications and to shape the future of regenerative medicine. Organoid technology is amongst these major developments, derived from primary tissues or more recently, from induced pluripotent stem cells (iPSC). The use of iPSC technology offers the possibility of cancer modeling especially in hereditary cancers with germline oncogenic mutations. Similarly, it has the advantage to be amenable to genome editing with introduction of specific oncogenic alterations using CRISPR-mediated gene editing. In the field of regenerative medicine, iPSC-derived organoids hold promise for the generation of future advanced therapeutic medicinal products (ATMP) for organ repair. Finally, it appears that they can be of highly useful experimental tools to determine cell targets of SARS-Cov-2 infections allowing to test anti-Covid drugs. Thus, with the possibilities of genomic editing and the development of new protocols for differentiation toward functional tissues, it is expected that iPSC-derived organoid technology will represent also a therapeutic tool in all areas of medicine.

Signal processing and generation of bioactive nitric oxide in a model prototissue

“…For example, given that enzyme processing in the tubular prototissue-like vessels can be regulated by employing different spatial sequences of the enzyme-CV-containing hydrogel modules, it seems feasible that the prototissue models could be individually designed for integration into biomedical and pharmaceutical applications involving glucose-mediated metabolic pathways. Moreover, designing synthetic prototissues with bespoke shape, size, spatial configuration and micro-anatomy could provide a route to artificial constructs that complement the use of organoids as therapeutic models in regenerative medicine 54 , or serve as micro-reactor-based implants for diagnostic, therapeutic, and theranostic applications.…”

Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids

“…Our study addressed this problem by studying cardiac signaling in an iPSC-derived heart organoid model that enables the recapitulation of disease phenotypes in a developing organoid that matches with fetal cardiac tissue at the cellular, structural and transcriptomic levels (Lewis-Israeli et al, 2021). iPS cells (Takahashi and Yamanaka, 2006;Takahashi et al, 2007) have introduced revolutionary concepts in precision medicine through the potential generation of organoids that can recreate developmentally relevant models under fully defined, reproducible, and efficient conditions (Turhan et al, 2021). This study used a differentiation protocol published by Lewis-Israeli and colleagues to produce human mini hearts composed of organoidderived cardiac myocytes (oCMs), endothelial cells (oECs), endocardial cells (oEnCs), epicardial cells (oEPI), and cardiac fibroblasts (oCFs).…”

Lung Organoids as Model to Study SARS-CoV-2 Infection

“…At the same time, organoid models are also needed to study the efficacy and toxicity of these drugs [ 91 ]. Large-scale current good manufacturing practice (cGMP) grade production of organoids enables the future manufacture of “transplantable” organoids and tissues, opening up the potential of organoids as advanced therapy medicinal products (ATMPs) [ 99 ]. Currently, multi-organoid systems have also been developed in which each organoid is located within specific compartments that are interconnected by microchannels and mimic the body’s systemic blood circulation, organ proximity, and function [ 91 ].…”