Current status and prospects of organoid-based regenerative medicine

Abstract

Organoids derived from stem cells or organ-specific progenitors are self-organizable, self-renewable, and multicellular threedimensional (3D) structures that can mimic the function and structure of the derived tissue. Due to such characteristics, organoids are attracting attention as an excellent ex vivo model for drug screening at the stage of drug development. In addition, since the applicability of organoids as therapeutics for tissue regeneration has been embossed, the development of various organoids-based regenerative medicine has been rapidly progressing, reaching the clinical trial stage. In this review, we give a general overview of organoids and describe current status and prospects of organoid-based regenerative medicine, focusing on organoid-based regenerative therapeutics currently under development including clinical trials. [BMB Reports 2023; 56(1): 10-14].

Fig. 1

Definition of organoid. An organoid is in vitro miniaturized and simplified three-dimensional (3D) structure having multiple organ-specific cell types constituting the organ. For example, intestinal organoids are composed of enterocytes, Paneth ells, goblet cells, enteroendocrine cells and stem cells (Lgr5+ crypt base columnar cells), which constitute the actual intestinal epithelium. In addition, organoid have organ-like structures (e.g., crypt and villus structures in intestinal organoids) and mimic their specific functions (e.g., secretory and absorptive functions in intestinal organoids).

Fig. 2

Application of organoids. Organoids can be used as regenerative medicine for damaged tissues or for in vitro disease modeling to test the efficacy/toxicity of new drugs. For example, colon organoids can be transplanted into colon ulcer to reconstruct the colon epithelium (Left), and the advanced in vitro model system of cancer organoids with immune cells can be used to test the efficacy of drugs such as cancer immunotherapy (Right).

Fig. 3

Repair of mucosal epithelium by colon organoid transplantation in radiation proctitis. (A) Fluorescence endoscopic tracing and (B) histological analysis of mouse colon organoid (Green) engrafted tissue at 4 weeks after transplantation. The mucosal epithelium damaged by radiation was structurally restored by engraftment of colon organoid transplantation. (C) Unsupervised clustering of scRNA-seq data from normal and colon organoid transplanted. (D) Proportion of cells (Enterocyte, Goblet cells, Paneth cells, Enteroendocrine cells, Tuft cells and CBCs: Crypt-base columnar cells) in normal and colon organoid TP tissue. TP; transplantation (Jee et al. Biomaterials. 2021).

Fig. 4

Salivary gland organoid as a therapeutic strategy for the xerostomia. (A) The therapeutic strategy of hSGO for radiation-induced xerostomia. (B) Engraftment of hSGO at 2, 4 weeks after transplantation in the radiation induced mouse xerostomia model. hSGO; human salivary gland organoid, TP; transplantation, hNu; human nucleoli, hE-cad; human E-cadherin.