Stem Cells and Organoid Technology in Precision Medicine in Inflammation: Are We There Yet?

Abstract

Individualised cellular models of disease are a key tool for precision medicine to recapitulate chronic inflammatory processes. Organoid models can be derived from induced pluripotent stem cells (iPSCs) or from primary stem cells ex vivo. These models have been emerging over the past decade and have been used to reconstruct the respective organ-specific physiology and pathology, at an unsurpassed depth. In cancer research, patient-derived cancer organoids opened new perspectives in predicting therapy response and provided novel insights into tumour biology. In precision medicine of chronic inflammatory disorders, stem-cell based organoid models are currently being evaluated in pre-clinical pharmacodynamic studies (clinical studies in a dish) and are employed in clinical studies, e.g., by re-transplanting autologous epithelial organoids to re-establish intestinal barrier integrity. A particularly exciting feature of iPSC systems is their ability to provide insights into organ systems and inflammatory disease processes, which cannot be monitored with clinical biopsies, such as immune reactions in neurodegenerative disorders. Refinement of differentiation protocols, and next-generation co-culturing methods, aimed at generating self-organised, complex tissues in vitro, will be the next logical steps. In this mini-review, we critically discuss the current state-of-the-art stem cell and organoid technologies, as well as their future impact, potential and promises in combating immune-mediated chronic diseases.

Standardizing Patient-Derived Organoid Generation Workflow to Avoid Microbial Contamination From Colorectal Cancer Tissues

“…Moreover, it has been shown that the use of antibiotics impacts cell transcriptional activity (42) and differentiation (43). These alterations impact cellular hierarchy within the organoids and affect stem cell viability and growth rate, whose functionality is at the basis of organoid generation (40,(44)(45)(46). Indeed, ChIP-seq analysis of H3K27ac identified approximately 10,000 sites that were enriched near genes involved in cell differentiation, tRNA modification, nuclease activity, and protein dephosphorylation, in cells treated with P/S (42).…”

Classic mechanisms and experimental models for the anti‐inflammatory effect of traditional Chinese medicine

“…In particular, organoid models are considered to be the closest in vitro model to simulate the in vivo physiological and pathological characteristics of diseases. 92 At present, organoid models of the intestines, lung, liver and stomach have been widely applied in the study of inflammation. As previously reported, organoid models have been used to evaluate the protective effect of TCM on intestinal damage (Glycyrrhetinic acid from Glycyrrhiza uralensis Fisch.…”

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

“…First, customization of organoids in a reproducible manner demands extreme precision in standardization even in the presence of engineered matrices, while it is almost impossible using poorly defined decellularized extracellular matrices. Achieving the reproducibility level fitful for clinical bio-translation of the organoids requires the mandatory following of good manufacturing practices like the other pharmaceutical products, stringent specification of the ingredient as well as critical quality attributes of the customized organoids, and strict adherence to the predefined bioprocessing methods, customization protocols, and ethical guidelines approved by any international regulatory authorities ( Kim et al, 2020 ; Tran et al, 2020 ). Even the methods for scalability should comply with the international standard.…”

“…Third, complete differentiation and full maturation of the organoid under the in vitro system often remain beyond the scope ( Truskey, 2018 ; Xu et al, 2018a , b ). Inadequate supply of nutrients, growth factors, and bioactive molecules, poor gaseous exchange, and stagnation of the wastes often limit the differentiation and maturation process ( Tran et al, 2020 ). Customization of organoids along with vasculatures using microfluidics platform or 3D bioprinting method or co-customization with blood-vessel organoid or fused organoid provides the promising means to overcome the limitation ( Ao et al, 2020 ; Chen et al, 2020 ; Zhang et al, 2020 ; Daly et al, 2021 ).…”

“…Prevascularized organoid constructs with a connected luminal network on microfluidic platforms or organoid-on-a-chip modules can restore the physiological flow to facilitate drug penetration and subsequent biodistribution ( Kim et al, 2020 ). Seventh, the bioactive components of matrix materials and media may alter metabolic and gene expression and signaling pathways of the organoid system ( Tran et al, 2020 ). Again, stringent regulatory control over the organoid customization components and protocols can solve the issue to a significant extent.…”