Disease Modeling in Stem Cell-Derived 3D Organoid Systems

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“…Advances in generating tumoroids from pancreatic cancer [20], glioblastoma [21], prostate cancer [22,23] and colorectal cancer [3] reveal that patient-derived tumoroids recapitulate patient-specific histological features. These tumoroids can also be cryopreserved in a similar manner as continuous cell lines and can subsequently be characterized by genomics, transcriptomics and using high-throughput in vitro drug screening assays, something that has spurred initiatives to develop live patient-derived tumoroid biobanks [1]. It is possible that data from tumoroid drug screening assays not only will complement and corroborate tumor genomic data but may in addition provide prediction on drug responses where sequencing data alone might fall short.…”

“…Although the methodology to establish tissue in vitro cultures has been available for more than a century [1], the use of two dimensional (2D) culture techniques to establish continuous tumor cell lines from explanted tumor tissue cultures is hampered by artificial culture conditions that severely diminish the success rate, and tumor clonal heterogeneity. Further, time constraints render this approach impractical for clinical application to derive drug response profiles of tumors for specific patients.…”

Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells

“…A way forward to overcome this limitation might be the use of organoids, self-organizing in vitro structures that include multiple cell types and mimic the in vivo architecture of an organ 30 . Despite the relative success in generating organoids mimicking development of the cerebral cortex (reviewed in 30,31 ), only one study has thus far reported the generation of cerebellar organoids.…”

“…Despite the relative success in generating organoids mimicking development of the cerebral cortex (reviewed in 30,31 ), only one study has thus far reported the generation of cerebellar organoids. Muguruma et al showed that the addition of Fgf19 and stromal cell-derived factor 1 (Sdf1) during differentiation promoted the self-organisation of human ESCs into polarized three-layer structures reminiscent of the human embryonic cerebellum 23 .…”

“…To overcome this, cerebellar organoids could be grown in spinning bioreactors to prolong their viability by improving nutrient and gas exchange 32 . Alternatively, the self-induction approach could be used to generate progenitors of various cerebellar subtypes, which could subsequently be plated onto biodegradable scaffolds to support their organization into a layered three-dimensional structure 30 . In such a system, microenvironmental niches surrounding progenitors have been shown to promote terminal differentiation and neuronal circuit formation 28 …”