Pancreatic 3D Organoids and Microfluidic Systems-Applicability and Utilization in Surgery: A Literature Review

Abstract

Background: Pancreatic organoids are a rapidly advancing field of research with new discoveries being made every day. A literature review was performed to answer the question of how relevant 3D pancreatic organoids are for surgery. Materials and Methods: We started our investigation by identifying articles in PubMed within the last 5 years using the keywords (("pancreatic organoid", OR "organ-on-a-chip", OR "pancreatic chip" OR "3D culture methods") AND pancreatic surgery). Only English articles were included in this literature review. This literature review was performed in a non-systematic way; articles were chosen without a predetermined protocol of inclusion and were based on the aim of the review. Results and Conclusions: There are many promising innovations in the field of 3D cultures. Drug sensitivity testing in particular holds great potential for surgical application. For locally advanced PDAC, EUS-FNB obtained cancer tissue can be cultured as organoids, and after 4 weeks, neoadjuvant treatment could be adjusted for each patient individually. Utilizing this approach could increase the number of R0 resections and possibly cure the disease. Furthermore, microfluidic devices, as a platform for pancreatic islet pre-transplant evaluation or cultivation of beta cells derived from HiPSC in vitro, promise broad application of islet transplantation to T1DM patients in the near future.

Keywords: PDAC; organ-on-a-chip; organoid; pancreatic organoids.

Figure 1

Advantages of different cell culturing methods: 3D organoid vs. 2D monolayer. Two-dimensional monolayers of cells have unlimited access to ECM ingredients, suffer less from hypoxia, and are simple to cultivate. Three-dimensional organoids are more complex structures with cell–cell and cell–matrix interaction, as well as possible growth in every direction. Created with BioRender.com.

Figure 2

Applications for 3D organoids. After PDAC biopsy, 3D cultures of cancer cells can be established. If pharmacotyping is successful, personalized chemotherapy or immunotherapy can be initiated. HiPSC can be differentiated to mature beta cells followed by same-size organoid formation in microfluidic devices with subsequent islet transplantation into the portal vein. Pancreatic cancer or islet organoids can be co-cultured with other cells in vitro to create a multiple organ-on-a-chip model for further drug or cell biology research. Created with BioRender.com.