Disease relevance of Organoids

• To examine the role of the retinoblastoma protein (pRB) in this process, we created human mammary epithelial cells (HMEC) deficient for pRB by infecting primary outgrowth from breast organoids with the human papillomavirus type 16 (HPV16) E7 gene [1].
• Histologic subtypes included well-differentiated thymic carcinoma in 19 (59%), high-grade carcinoma in 6 (19%), organoid thymoma in 4 (13%), and cortical thymoma in 3 (9%) according to the Marino and Müller-Hermelink classification [2].
• In vitro endothelial cell tubulogenesis induced by isolated mammary organoids or carcinoma in situ from DMBA-treated rats is inhibited by ZD6474, in a dose-dependent fashion [3].
• Mucin-producing carcinomas were classified into two groups: the ordinary duct cell carcinoma group and a group that showed marked atrophy and extensive fibrosis of the parenchyma, a lack of organoid differentiation and gastric mucins, and an abundance of large and small intestinal mucins [4].
• The presence of follicular lymphoid hyperplasia, either within the tumor, in the residual normal thymus, or in both, was a significant predictor of myasthenia gravis (P < .0015); there was an increased association of myasthenia gravis and thymomas with cortical type epithelium (organoid thymoma, cortical thymoma, and WDC) [5].

High impact information on Organoids

• To determine the adhesion molecules involved in organoid formation we attempted to block this process by single cell suspensions of LIM 1863 reseeded in the presence of monoclonal antibodies [6].
• Endothelium-dependent relaxations were also studied after incubation with L-arginine, L-sepiapterin, and liposome-entrapped superoxide dismutase (SOD) and after organoid culture with cis-vaccenic acid [7].
• Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo [8].
• Several EGFR agonists also stimulated Adam17(-/-) mammary organoid growth in culture, but only AREG was expressed abundantly in the developing ductal system in vivo [9].
• HFH cultures maintained for 9 to 12 months produced grossly visible organoids containing ductular structures that stained for CK18, CK19, and AFP [10].

Biological context of Organoids

• In medium MCDB 170, which was developed for long-term growth of human mammary epithelial cells from reduction mammoplasty organoids, cells from the basal layer proliferate, while in MM medium the basal phenotype dominates, but a few cells with the luminal phenotype are found [11].
• This expression was induced primarily by prolactin in mammary gland organoids and was similar to alpha s1-casein gene expression in vivo [12].
• We also examined the effects of FGF7 on Matrigel-embedded organoids, containing both epithelial and myoepithelial cells, and showed FGF7 induced an increase in cellular proliferation [13].
• Dexamethasone induces chondrogenesis in organoid culture of cell mixtures from mouse embryos [14].
• The diagnosis of neuroendocrine (NE) lung tumor is dependent on a number of observations: organoid structure, dense core granules, and various molecular components, including chromogranin A, neurosecretory enolase, synaptophysin, neural cell adhesion molecules, and others [15].

Anatomical context of Organoids

• The hepatocyte organoids were functional as judged by the high level of albumin secretion and accumulation of bilirubin [16].
• Interestingly, when mammary gland samples from the same animals were obtained from pure epithelial organoid preparations, no differences in telomerase activity could be distinguished between animals or groups [17].
• IEC were digested from intestinal fragments as small intact units of epithelium (organoids) by using collagenase and dispase [18].
• Addition of hormones was required to maintain low levels of Wap mRNA in organoids cultured on reconstituted basement membrane, however, Wap mRNA was not induced [19].
• To create vascularized organoids, we transplanted 800 mouse islets into polyvinyl alcohol (PVA) or polyglycolic acid (PGA) polymers in subcutaneous tissue of streptozocin-diabetic mice either immediately (four in PVA and six in PGA) or 7 days (four in PVA and four in PGA) after implantation [20].

Associations of Organoids with chemical compounds

• By contrast, no effect of estradiol could be evidenced on the [35S]methionine-labeled proteins released into the medium by the organoids [21].
• Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids [22].
• Sorted RMEC subpopulations, unsorted mixed cells, and undispersed organoids were seeded in Matrigel and cultured in either a complete hormone medium (CHM) with 10% fetal bovine serum, progesterone, estradiol, hydrocortisone, insulin, and prolactin or a serum-free medium containing EGF, insulin, hydrocortisone, and human transferrin [23].
• The stimulatory effect of Ang II was much more pronounced in intact organoids that in endothelium-denuded organoids, indicating synergistic growth regulation by Ang II and endothelium-derived factors [24].
• However, for endothelium-denuded organoids, medial [3H]-thymidine incorporation in the combined presence of Ang II and cilazaprilat was not significantly different from that in untreated controls [24].

Gene context of Organoids

• Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids [25].
• We further demonstrated that MDCK cells that express mutant EGFR that are competent in c-Src recruitment lose epithelial polarity in organoid cultures, whereas cells overexpressing the wild-type EGFR retain a polarized phenotype [26].
• Microscopic examination revealed a fibroepithelial tumor formed by an organoid pattern of ductal structures with a very striking stromal appearance composed of extensive vascular proliferation and that demonstrated strong immunoreactivity for CD31, CD34, and Factor VIII [27].
• Short term organoid cultures of both normal veins and human arteriosclerotic plaque also expressed tissue-associated IL1 activity upon stimulation with LPS but did not release significant soluble IL1 activity [28].
• Isolated mammary organoids produced a 'stellate' type colony when PRL + P were present in the culture medium [29].

Analytical, diagnostic and therapeutic context of Organoids

• RESULTS: Prominent Gal-1 staining coincided with SMC proliferation in human coronary endarterectomy samples in organoid culture [30].
• Three such models are described, including whole organ culture, mammary epithelial cell (MEC) organoids, and MEC-stromal cocultures [31].
• When constriction during organoid culture was inhibited with papaverin or verapamil, inward remodeling was fully prevented: 184 +/- 6.3 to 184 +/- 5.8 microm for papaverin (n = 6) and 174 +/- 5.5 to 177 +/- 7.4 microm for verapamil (n = 6) [32].
• The organoids secreted intact parathyroid hormone (PTH) and COOH-terminal hormone fragments which were similar to those released from monolayer cell cultures [33].
• The mass in the left upper lobe (LUL) was a tubular adenocarcinoma with neuroendocrine features including organoid nests showing occasional rosette formation, nuclear palisading in the periphery of the nests and positive immunoreaction for CD56, chromogranin A and synaptophysin [34].

References