Bioprinted pluripotent stem cell-derived kidney organoids provide opportunities for high content screening

Abstract

Recent advances in the directed differentiation of human pluripotent stem cells to kidney brings with it the prospect of drug screening and disease modelling using patient-derived stem cell lines. Development of such an approach for high content screening will require substantial quality control and improvements in throughput. Here we demonstrate the use of the NovoGen MMX 3D bioprinter for the generation of highly reproducible kidney organoids from as few as 4,000 cells. Histological and immunohistochemical analyses confirmed the presence of renal epithelium, glomeruli, stroma and endothelium, while single cell RNA-Seq revealed equivalence to the cell clusters present within previously described organoids. The process is highly reproducible, rapid and transferable between cell lines, including genetically engineered reporter lines. We also demonstrate the capacity to bioprint organoids in a 96-well format and screen for response to doxorubicin toxicity as a proof of concept for high content compound screening.

Organovo is collaborating with the University of Virginia to develop 3D bioprinted tissues for volumetric muscle loss injury

Organovo Holdings, Inc. (NASDAQ:ONVO) (“Organovo”), a three-dimensional biology company focused on delivering scientific and medical breakthroughs using its 3D bioprinting technology, today announced a collaboration with the University of Virginia to develop 3D bioprinted tissues for volumetric muscle loss (“VML”) injury. The research will take place in the laboratory of George J. Christ, Ph.D., professor of biomedical engineering and orthopaedic surgery at UVA.

Organovo is collaborating with the National Center for Advancing Translational Sciences and the National Eye Institute of Health to develop better and more clinically predictive tissue models using 3D bioprinted functional eye tissue

Organovo announced today that they are joining together with two institutes from the National Institutes of Health (NIH) to help scientists develop more reliable tools for bringing safer, more effective treatments to patients on a faster timeline. Organovo is collaborating with the National Center for Advancing Translational Sciences (NCATS) and the National Eye Institute (NEI) to develop better and more clinically predictive tissue models using Organovo’s NovoGen MMX Bioprinter®. Organovo will collaborate with NCATS and NEI in using the NovoGen Bioprinting platform to create three-dimensional, architecturally correct, functional living tissues.

Organovo and Yale School of Medicine, Department of Surgery have formed a collaboration to develop bioprinted tissues for surgical transplantation research

Organovo Holdings, Inc. (NYSE MKT: ONVO) (“Organovo”), a three-dimensional biology company focused on delivering breakthrough 3D bioprinting technology, and Yale School of Medicine, Department of Surgery have formed a collaboration to develop bioprinted tissues for surgical transplantation research, made possible by a generous gift from the Methuselah Foundation.

Modeling tumor phenotypes in vitro with three-dimensional bioprinting

The tumor microenvironment plays a critical role in tumor growth, progression, and therapeutic resistance, but interrogating the role of specific tumor-stromal interactions on tumorigenic phenotypes is challenging within in vivo tissues. Here, we tested whether three-dimensional (3D) bioprinting could improve in vitro models by incorporating multiple cell types into scaffold-free tumor tissues with defined architecture. We generated tumor tissues from distinct subtypes of breast or pancreatic cancer in relevant microenvironments and demonstrate that this technique can model patient-specific tumors by using primary patient tissue. We assess intrinsic, extrinsic, and spatial tumorigenic phenotypes in bioprinted tissues and find that cellular proliferation, extracellular matrix deposition, and cellular migration are altered in response to extrinsic signals or therapies. Together, this work demonstrates that multi-cell-type bioprinted tissues can recapitulate aspects of in vivo neoplastic tissues and provide a manipulable system for the interrogation of multiple tumorigenic endpoints in the context of distinct tumor microenvironments.