Disease Modeling in Stem Cell-Derived 3D Organoid Systems

Organoids can be developed from pluripotent stem cells and adult stem cells. Organoids have been established for multiple organs including intestine, kidney, brain, liver, stomach, pancreas, ovary, and lung. Organoids can be used in multiple clinical applications including disease modeling, drug screening, host–microbe interactions, and regenerative therapy. Patient-derived organoids may enable personalized medicine. Genes can be manipulated within organoids using molecular technologies such as the lentiviral expression system and CRISPR/Cas9; this may enable disease modeling and targeted gene therapy. The complex interplay between microbes – bacteria, parasites, and viruses – and the host epithelium have been dissected using organoids derived from brain, stomach, and intestine. Mechanically dynamic designer matrices such as hybrid polyethylene glycol hydrogels might expand the applicability of organoids in the future. Organoids are 3D in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture, functionality, and genetic signature of original tissues. Thus, organoid technology has been rapidly applied to understanding stem cell biology, organogenesis, and various human pathologies. The recent development of human patient-derived organoids has enabled disease modeling with precision, highlighting their great potential in biomedical applications, translational medicine, and personalized therapy. In light of recent breakthroughs using organoids, it is only apt that we appreciate the advantages and shortcomings of this technology to exploit its full potential. We discuss recent advances in the application of organoids in studying cancer and hereditary diseases, as well as in the examination of host cell–microorganism interactions. Organoids are 3D in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture, functionality, and genetic signature of original tissues. Thus, organoid technology has been rapidly applied to understanding stem cell biology, organogenesis, and various human pathologies. The recent development of human patient-derived organoids has enabled disease modeling with precision, highlighting their great potential in biomedical applications, translational medicine, and personalized therapy. In light of recent breakthroughs using organoids, it is only apt that we appreciate the advantages and shortcomings of this technology to exploit its full potential. We discuss recent advances in the application of organoids in studying cancer and hereditary diseases, as well as in the examination of host cell–microorganism interactions. organ-specific stem cells found in adult organisms which have the ability to divide, renew, and regenerate tissue. a cellular self-destruct mechanism to eliminate dysfunctional components in cytosolic organelles such as the lysozyme. a large collection of comprehensive biological tissue samples or medical records for research purposes. the intestinal epithelium is lined by self-renewing crypt–villus units. Villi are protrusions that include differentiated cells. The crypt is the invaginating region and is composed of proliferating Lgr5+ stem cells and transit-amplifying cells. a genetic disorder affecting mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and excessive mucus production as well as frequent lung infections. 3D aggregates of pluripotent stem cells (PSCs), specifically embryonic stem cells (ESCs) from blastocysts of humans, mice, and primates. embryonic stem cells are PSCs derived from the inner cell mass of the blastocyst of an early-stage preimplantation embryo. a highly conserved methyltransferase that targets lysine 27 of histone H3A and is commonly associated with the silencing of genes involved in differentiation; often overexpressed in prostate and breast cancer. brain tumor aggressiveness has been associated with different hypoxia levels in the tumor microenvironment. They can modulate the maturity of the tumor mass. pluripotent stem cells derived from adult somatic cells by reprogramming to an embryonic stem cell-like state. The first iPSCs were created from mouse embryonic fibroblasts (MEFs) and skin fibroblasts by the introduction of transcription factors Oct4, Sox2, Klf4, and c-Myc, commonly known as Yamanaka factors. Nanog and Lin28 can be used as replacements for Klf4 and c-Myc to reprogram human cells. a group of inflammatory conditions affecting the colon and small intestine. Crohn’s disease and ulcerative colitis are the primary types of IBD. Lgr5 (leucine-rich repeat-containing G protein-coupled receptor 5), also known as G protein-coupled receptor 49 (GPR49), is a receptor for R-Spondin. Lgr5 is a marker of adult stem cells in particular tissues including intestine, stomach, liver, pancreas, hair follicle, kidney, and taste bud; these are known as Lgr5+ stem cells. the entire content of metabolites present within an organism, cell, or tissue. the entire collection of microorganisms in a specific niche such as the human gut. The microbiome comprises all the genetic material within a microbiota. a device in which a biological reaction is carried out under defined conditions. Spinning bioreactors are used for 3D cell cultures by mixing the oxygen and nutrients in the medium using a constant state of motion. a type of exocrine pancreatic cancer originating from cells lining in pancreatic duct. located at the base of the crypts of Lieberkühn in the small intestine, they synthesize and secrete substantial quantities of antimicrobial peptides and proteins, thus providing host defense against microbes. proteins expressed by cells of the innate immune system that can identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), associated with microbial pathogens; and damage-associated molecular patterns (DAMPs), associated with cell components released during cell damage or death. They are classified into four types: Toll-like receptors (TLRs), nucleotide oligomerization domain receptors (NLRs), C-type lectin receptors (CLRs), and RIG-1-like receptors (RLRs). transfer of primary tumor tissue from patients into an immunodeficient mouse. PDTX generates preclinical models that facilitate the study of metastasis and drug screening. self-renewing stem cells with the ability to differentiate into any type of cell of all three germ layers – ectoderm, endoderm, and mesoderm. PSCs include both embryonic stem cells (ESCs) and induced PSCs (iPSCs). the total spectrum of protein that is expressed by a cell, tissue, or organism. ligand of the Lgr4, 5, and 6 receptors. The R-spondin–Lgr5 (or Lgr4 and 6) complex inhibits Wnt repressors RNF43 or ZNRF3, resulting in Wnt signaling. end-products of fermentation of dietary fibers by the anaerobic intestinal microbiota in the intestine. They are considered to be the main nutrients for the lining cells of the large intestine and exert beneficial effects on mammalian energy metabolism. the sum total of all mRNA molecules expressed by a cell, tissue, or organism. aggregates of cancer cells in the form of spheroids or organoids formed in vitro. a flavivirus transmitted by Aedes species mosquitoes. It was first isolated from a rhesus monkey in the Zika forest of Uganda in 1947.