Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank

Abstract

Organoids are in vitro self-assembling, organ-like, three-dimensional cellular structures that stably retain key characteristics of the respective organs. Organoids can be generated from healthy or pathological tissues derived from patients. Cancer organoid culture platforms have several advantages, including conservation of the cellular composition that captures the heterogeneity and pharmacotypic signatures of the parental tumor. This platform has provided new opportunities to fill the gap between cancer research and clinical outcomes. Clinical trials have been performed using patient-derived organoids (PDO) as a tool for personalized medical decisions to predict patients’ responses to therapeutic regimens and potentially improve treatment outcomes. Living organoid biobanks encompassing several cancer types have been established, providing a representative collection of well-characterized models that will facilitate drug development. In this review, we highlight recent developments in the generation of organoid cultures and PDO biobanks, in preclinical drug discovery, and methods to design a functional organoid-on-a-chip combined with microfluidic. In addition, we discuss the advantages as well as limitations of human organoids in patient-specific therapy and highlight possible future directions.

The Effects of Transforming Growth Factor-β1 on the Differentiation of Cell Organoids Composed of Gingiva-Derived Stem Cells

“…The advantage of the organoid model is the application of stem cells without the use of scaffolds [ 38 ]. Organoids can be fabricated from participants with healthy or diseased conditions and can mimic individual conditions [ 9 ]. Lineage-specific organoids have been fabricated and tested for cardiac regeneration [ 39 ].…”

“…Furthermore, no statistically significant differences were demonstrated in the group treated with transforming growth factor-β compared with longer incubation times on days 9 and 11 (P > 0:05). with healthy or diseased conditions and can mimic individual conditions [9]. Lineage-specific organoids have been fabricated and tested for cardiac regeneration [39].…”

“…Organoids made from human teeth demonstrated epithelial stemness phenotypes and differentiation potential with long-term expandability [ 8 ]. Organoids possess cellular structures which maintain and provide stability to the key characteristics of the targeted organs [ 9 ]. Historically, dentin-pulp-like organoids displaying stem cell-like and odontoblastic characteristics have been developed and have been tested for tooth regeneration [ 10 ].…”

“…Organoids made from human teeth demonstrated epithelial stemness phenotypes and differentiation potential with long-term expandability [8]. Organoids possess cellular structures which maintain and provide stability to the key characteristics of the targeted organs [9].…”

Functional Precision Oncology: The Next Frontier to Improve Glioblastoma Outcome?

“…PDOs conserve tumor heterogeneity and TME components, tissue architecture, molecular and functional features. PDOs can be efficiently expanded over time while conserving patient-specific genomic features and intra-tumor heterogeneity, which could be reliably correlated with functional responses to therapeutics [ 48 ]. Non-malignant cells that are retained after 2 weeks of culture in the GBM organoid models include macrophage/microglia, T-cells, stromal cells and oligodendrocytes [ 49 ].…”