The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update

Abstract

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.

Cell Therapy: Types, Regulation, and Clinical Benefits

“…Currently a hot topic in translational stem cell research, PSC- and ASC-derived organoids are highlight-worthy. Despite pending clinical investigations, these organoids hold promise as future regenerative medicine applications by offering in vitro three dimensional (3D) structural and functional mimicry of organs ( 98 ). Originally, these organoids are patient-derived stem cells manipulated and grown in controlled media formulations to dictate their differentiation, then propagated into 3D structures/matrices ( 99 ).…”

Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids

“…However, some biological aspects are unique to humans, and as a consequence, these models show limitations recapitulating human pathology. In that sense, PDOs emerged as a model to study cancer, infectious diseases, and inheritable genetic disorders [ 10 , 11 , 12 , 13 ]. The generation of organoids requires the use of stem cells, which can be either (a) pluripotent stem cells (PSCs)—embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs)—or (b) adult stem cells (ASCs) [ 7 , 8 , 9 , 13 ].…”

“…The development of the organoids requires the use of specific growth factors depending on the tissue of origin, and they are mainly restricted to the growth of epithelial cells [ 14 ]. For that reason, the ASC-derived organoids are less complex than the iPSCs-derived, which might include mesenchymal and epithelial constituents [ 12 ]. On the other hand, tissue-derived organoids may recapitulate the genetic and epigenetic signature of the original organ [ 14 ], but iPSCs can lose this kind of information due to the dedifferentiation process required for the establishment of the cell line [ 15 ], thus hampering the use of iPSCs for preclinical models.…”

Organoids: An Emerging Tool To Study Aging Signature Across Human Tissues. Modeling Aging With Patient-derived Organoids

“…However, some biological aspects are unique to humans and as a consequence, these models show limitations recapitulating human pathology. In that sense, PDOs emerged as a model to study cancer, infectious diseases and inheritable genetic disorders [10][11][12][13]. The generation of organoids requires the use of stem cells which can be either (a) pluripotent stem cells (PSCs) -embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs) -or (b) adult stem cells (ASCs) [7][8][9]13].…”

“…Development of the organoids require the use of specific growth factors depending on the tissue of origin and are mainly restricted to the growth of epithelial cells [14]. For that reason, the ASC-derived organoids are less complex than the iPSCs-derived which might include mesenchymal and epithelial constituents [12]. On the other hand, tissue derived organoids may recapitulate the genetic and epigenetic signature of the original organ [14] but iPSCs can lose this kind of information due to the dedifferentiation process required for the establishment of the cell line [15] thus hampering the use of iPSCs for preclinical models.…”