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Engineered materials to model human intestinal development and cancer using organoids.

ABSTRACT: Human organoids provide constructive in vitro models of human development and disease, as these recapitulate important morphogenetic and functional features of the tissue and species of origin. However, organoid culture technologies often involve the use of biologically-derived materials (e.g. Matrigel™) that do not allow dissection of the independent contributions of the biochemical and biophysical matrix properties to organoid development. Additionally, their inherent lot-to-lot variability and, in the case of Matrigel™, tumor-derived nature limits their applicability as platforms for drug and tissue transplantation therapies. Here, we highlight recent studies that overcome these limitations through engineering of novel biomaterial platforms that (1) allow to study the independent contributions of physicochemical matrix properties to organoid development and their potential for translational therapies, and (2) better recreate the tumor microenvironment for high-throughput, pre-clinical drug development. These studies illustrate how innovative biomaterial constructs can contribute to the modeling of human development and disease using organoids, and as platforms for development of organoid-based therapies. Finally, we discuss the current limitations of the organoid field and how they can potentially be addressed using engineered biomaterials.

SUBMITTER: Cruz-Acuna R

PROVIDER: S-EPMC6408969 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Engineered materials to model human intestinal development and cancer using organoids.

Cruz-Acuña Ricardo R García Andrés J AJ

Experimental cell research 20190219 1-2

Human organoids provide constructive in vitro models of human development and disease, as these recapitulate important morphogenetic and functional features of the tissue and species of origin. However, organoid culture technologies often involve the use of biologically-derived materials (e.g. Matrigel™) that do not allow dissection of the independent contributions of the biochemical and biophysical matrix properties to organoid development. Additionally, their inherent lot-to-lot variability an ...[more]

PMID: 30794801

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Project description:UnlabelledDirected differentiation of stem cell lines into intestine-like tissue called induced human intestinal organoids (iHIOs) is now possible (J. R. Spence, C. N. Mayhew, S. A. Rankin, M. F. Kuhar, J. E. Vallance, K. Tolle, E. E. Hoskins, V. V. Kalinichenko, S. I. Wells, A. M. Zorn, N. F. Shroyer, and J. M. Wells, Nature 470:105-109, 2011). We tested iHIOs as a new model to cultivate and study fecal viruses. Protocols for infection of iHIOs with a laboratory strain of rotavirus, simian SA11, were developed. Proof-of-principle analyses showed that iHIOs support replication of a gastrointestinal virus, rotavirus, on the basis of detection of nonstructural viral proteins (nonstructural protein 4 [NSP4] and NSP2) by immunofluorescence, increased levels of viral RNA by quantitative reverse transcription-PCR (qRT-PCR), and production of infectious progeny virus. iHIOs were also shown to support replication of 12/13 clinical rotavirus isolates directly from stool samples. An unexpected finding was the detection of rotavirus infection not only in the epithelial cells but also in the mesenchymal cell population of the iHIOs. This work demonstrates that iHIOs offer a promising new model to study rotaviruses and other gastrointestinal viruses.ImportanceGastrointestinal viral infections are a major cause of illness and death in children and adults. The ability to fully understand how viruses interact with human intestinal cells in order to cause disease has been hampered by insufficient methods for growing many gastrointestinal viruses in the laboratory. Induced human intestinal organoids (iHIOs) are a promising new model for generating intestine-like tissue. This is the first report of a study using iHIOs to cultivate any microorganism, in this case, an enteric virus. The evidence that both laboratory and clinical rotavirus isolates can replicate in iHIOs suggests that this model would be useful not only for studies of rotaviruses but also potentially of other infectious agents. Furthermore, detection of rotavirus proteins in unexpected cell types highlights the promise of this system to reveal new questions about pathogenesis that have not been previously recognized or investigated in other intestinal cell culture models.

Dataset Information

Engineered materials to model human intestinal development and cancer using organoids.

Publications

Engineered materials to model human intestinal development and cancer using organoids.

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