See also Patient induced stem cells
Companies: Thermo Fisher Scientific (organoids such as OncoPro Tumoroid Cell oines, stemflex medium for robust expansion of pluripotent stem cells and Geltrex flex matrix for growth of cells in 3D culture) Merck KGaQ (Darmstadt, Germany). Danaher (involved in developing organoids) Charles River Laboratories (immune and vascular competent tumor organoids) Corning (3D organoid modesl) PNS-3D Organoids (composed of human iPSC dervied sensory neurons and primary Schwann cells co-cultured in a 3D matrix. Sensory neurons provide functional signaling capabilities, while Schwann cells support axonal growth and myelination. Together these cell types self-organize into structured nerve-like tissues that replciate key cellular interations of the peripheral nerve system). Millipore Sigma (patient dervied organoids)
Corning Life Sciences: —Corning Matrigel Matrix: is a solubilized basement membrane preparation. Rich in extracellular matrix proteins such as laminin and collagen, Matrigel Matrix is sued to produce hydogels that support organ/tissue architectures.
Introduction:
Organoids are derived from pluripotent stem cells or isolated organ progenitors that differentiate to form an organ-like tissue exhibiting multiple cell types that self-organize to form a structure not unlike the organ in vivo. Because organoids can be grown from human stem cells and from pateint derived induced pluripotent stem cells, they ahve the potential to model human development and disease. In addiition, they ahve potential for drug testing. Orgaonids have beome increasingly popular as tissue odels since they can retain the gentic and phenotypic heterogeneity of the orginal tissue.
Organoids can be assembled or allowed to self-assemble. In either case, they are typically cultured with specific growth factors and extracellular matrix proteins. This approach was pioneered in 2009, when researchers generated the first 3 D organoid culture form adult stemp cells.
The momentum behind regulatory shift i shown in the FDA approval in oncology based exclusively on efficacy data form human vascularized organoids, generated using a platform developed by Qureator.
The FDA has already approved the first IND submission supported soley through human vascularized organoid based combination studies, without relying on traditional animal efficacy testing (see SillaJen–Sorth Korea based developer of oncoytic virus immunotherapeutics) to begin clinical trails for a combination therapy, a dual inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK). (see NCT05768932)
Epithelial Organoids:
Clevers “Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium” Gastroenterology, 2011) estbalished long-term culture conditions under which single crypts or stem cells dervied form mouse small intestine expand over long periods. The expanding crypts undergo multiple crypt fission events, simultaneously generating villus-like epithelial domains that contain all differentiated tyeps of cells. They adapted the culture conditions to grwo similar epithelial organoids form mouse colon and human small intestine colon. Addition of Wnt3A to the combination of growth factors applied to mouse colon crypts allowed them to expand indefinitely. Addition of nicotinamide, along with a small molecule inhiibtor of Alk and an inhibitor of p38 were required for long-term culture of human small intestine and colon tissues. The technology can be used to study infected, inflammatory, or neoplastic tissues form the human gastrointestinal tract.
Lymphoid Organs:
Most of what is known about adaptive immunity has come from inbred mouse studies, using methods that are often difficult to confirm in humans. The B cells tht are responsible for forming a neutralizing antibody response develop within gemerinal centers (GCs) and extrafollicular regions in lumphoid organs. Upon antigen presentation by APCs, T follicular help (TFH) cells, and a variety of hematopoietic and non-hematopoietic cells interact and diliver signals to GC B cells for survival, proliferation, antibody affinity maturation, class switch recombination and differentation.
Davis “Modeling human adaptive immune resposnes with tonsil organoids” Nat Med. 2021) disclose using the widespread availability of human tonsils, lymphoid organs that are easily procured from tonsillectomy surgeries as discarded tissue, to develop an accessible system that replicates an antigen-specific adaptive immune response to a vaccine and supports key aspects of adaptive immunity. During an adaptive immune resposne, peripheral lympohoid organs like the tonsils, lymph nodes and spleed develop GCs. B cells congreegate in teh GC area, whereas T cells are largely in outlying areas. In the organoid cultures, GC like structures with distinct B and T cell rich aggregates in both LAIV stimulated an unstimualted cultures, started around 48 h after culture initiation. Activiton induced tyoidine deaminase (AID), which is required for both somatic hypermutation and class switching was expressed in these cultures.
Patient-derived organoids:
Genoskin (takes actual human skin obtained from surgical procedures and maintains that intact tissue ex vivo.)
Patient-dervie organoids offer a translational aligned alternative. Derived form adult stem cells and expanded as 3D mini organs in a dish, PDOs preserve key features of the originating specimen including histopathology, genomic landscape and functional drug response phenotypes.