Acoustic Droplet Printing Tumor Organoids for Modeling Bladder Tumor Immune Microenvironment within a Week

Abstract

Current organoid models are limited by the incapability of rapidly fabricating organoids that can mimic the immune microenvironment for a short term.Here, an acoustic droplet-based platform is presented to facilitate the rapid formation of tumor organoids, which retains the original tumor immune microenvironment and establishes a personalized bladder cancer tumor immunotherapy model. In combination with a hydrophobic substrate, the acoustic droplet printer can yield a large number of homogeneous and highly viable bladder tumor organoids in vitro within a week. The generated organoids consist of all components of bladder tumor, including diverse immune elements and tumor cells. By coculturing tumor organoids with autologous immune cells for 2 days, tumor reactive T cells are induced in vitro. Furthermore, it is also demonstrated that these tumor-reactive T cells can also enhance the killing efficiency of matched organoids. Because of the easy operation, repeatability, and stability, the proposed acoustic droplet platform will provide a reliable approach for personalized tumor immunotherapy.

The application of 3D bioprinting in urological diseases

“…could also yield bladder cancer organoids using an acoustic inkjet bioprinter, where mouse primary bladder tumor cells were cultured with immune cells in Matrigel with sized of 150–200 ​nL containing 6000 ​cells to retain the immune microenvironment similar to primary tissue for more than two weeks ( Fig. 7 B) [ 180 ]. The bioprinted co-culture system more realistically mimicked the TME and could be a novel in vitro model system for personalized immunotherapy.…”

Application of Patient-Derived Cancer Organoids to Personalized Medicine

“…There have also been some studies on immunotherapy using organoids [ 82 , 83 , 84 , 85 , 86 , 87 ]. Neal et al co-cultured primary tumor epithelial cells with endogenous syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit.…”

“…By co-culturing these tumor organoids with autologous immune cells, tumor-reactive T cells were induced in vitro. Furthermore, it has also been demonstrated that these tumor-reactive T cells enhance the killing efficiency of matched organoids [ 86 ]. Kholosy et al reported the procedure of a co-culturing system and drug assay of pediatric aggressive malignancies such as diffuse intrinsic pontine glioma or neuroblastoma organoids with immune cells [ 87 ].…”

Culture of patient-derived multicellular clusters in suspended hydrogel capsules for pre-clinical personalized drug screening

“…Existing PDTOs derived from primary liver tumor single cells and co-cultures with immune cells cannot completely recapitulate the tumor microenvironment (TME), such as the biomechanical characteristics of ECM; fibroblasts and vascular-related cells of stromal cells; immune cells; and non-cellular components [ [21] , [22] , [23] , [24] ]. Numerous studies have reported that the TME can significantly influence tumor progression [ 25 , 26 ].…”