Retinal Organoids as Lab Models for Retinoblastoma

Article: Retinoblastoma resource: Researchers create more accurate research model
Source: St. Jude Children's Research Hospital, via ScienceDaily  and NEI
Published: August 6, 2021

Retinoblastoma organoids

Retinoblastoma is a rare pediatric eye cancer driven by biallelic inactivation of the RB1  gene. Research into the pathophysiology of retinoblastoma, however, has had many limitations. First, rare eye diseases such as retinoblastoma have a small pool of patients to sample from. Genetically engineered mouse models of retinoblastoma do not express the abnormalities seen in humans when the RB1  gene is silenced, and are therefore not always reliable predictors for preclinical drug development. Biopsies in living patients are also contraindicated, since the act of biopsy can further spread the tumor cells. As such, tumor samples have been derived from more advanced stages requiring removal of the eyeball. Scientists are investigating the use of retinal organoid to more accurately model retinoblastoma to study the early stages of the disease as well as to screen for potential therapies. The researchers hope that these organoids could also shed light on other drivers of tumor development beyond the RB1  gene. In this case, the samples were collected from 15 retinoblastoma patients who had germline mutations in RB1, from which 3D cultures of cells were grown from induced pluripotent stem cells (iPSCs). These iPSCs developed into retinal organoids and were then injected into mouse eyes, where retinoblastomas subsequently formed. Whole-genome sequencing, RNA sequencing, and methylation analysis of these retinoblastoma tumors showed that they were indistinguishable from patient samples. The first author of the study comments on the novelty of the research, saying, “The ability of the organoid models to [successfully grow into organoids and later spontaneously developed into tumors] is unique, because cell lines with RB1  mutations do not spontaneously develop into retinoblastoma tumors.” Data from the project is freely available in the Childhood Solid Tumor Network at St. Jude Children's Research Hospital.

My rating of this study: ⭐⭐⭐

Norrie JL, Nityanandam A, Lai K, et al. "Retinoblastoma from human stem cell-derived retinal organoids." Nature Communications.  12:4535. 27 July 2021. https://doi.org/10.1038/s41467-021-24781-7