Bioengineering for intestinal organoid cultures

Abstract

Recent advances allow access to human cell-based intestinal organoids that recreate human physiology to levels not possible with conventional 2D cell cultures. Despite their huge potential, there are many challenges that remain. This review will cover recent bioengineering approaches to improve organoid maturation, scale up, reproducibility and analysis. The first section covers the advances in engineering the culture environment, followed by the section on tools for micro-manipulation and analysis of organoids. The last section reviews the computational models developed to guide the use of engineered materials and tools, and to interpret observed results as well. The ability to use organoids for discovery research, and the need to both exert exquisite experimental control and obtain quantitative measurements from organoid models means that the field is ripe for collaborative efforts between biologists, engineers, clinicians and industry.

Self‐Organizing Human Induced Pluripotent Stem Cell Hepatocyte 3D Organoids Inform the Biology of the Pleiotropic TRIB1 Gene

“…(24,34,35) Here we describe an efficient protocol using hiP-SCs for hepatic 3D organoid differentiation by using short exposure to a nonengineered matrix. In contrast to the engineered matrices such as polyethylene glycol, polyglycolic/poly-l-lactic acid, glycosaminoglycans, pullulan, synthetic scaffolds with collagen, fibrinogen and laminin commonly used for 3D organoid studies, (36,37) we used a short exposure to nonengineered laminin-enriched matrigel and CultureX (CultureX, Cambridge, MA) as a matrix for hepatic organoid differentiation. Studies are ongoing to further characterize these 3D organoids and improve the strategies to better obtain defined populations of nonparenchymal cells.…”

Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling

“…Known as 3D ex vivo cellular cultures, organoids form either through self-organization or directed assembly under specific organogenesis cues. [148] Organoids not only physically resemble the architecture, cellular organization, and composition of the original tissue, [149] they also recapture genetic signatures of their in vivo counterparts. [150] As compared with spheroids, organoids contain several cell spatially-restricted lineages of committed cell types generated from either pluripotent stem cells (PSCs) or organ-specific adult stem cells (ASCs).…”

“…While research with organoids mainly has focused on tissue engineering and regeneration, [148, 167] there is also a significant clinical need for biomimetic tumor models to bridge the technological gap between standard 2D cultures, 3D cultures such as spheroids, and in vivo models of cancer generated from established cell lines. However, compared to the large body of work using tumor spheroids, very few studies have attempted to engineer spatio-temporally organized organoid platforms to recapitulate complex tumor microenvironments.…”

In Vitro 3D Cultures to Reproduce the Bone Marrow Niche

“…To mimic human cancer growth, in vivo animal models are also widely used to study cancer cells. Animal models can provide a complex physiologic structure that is reasonably similar to the human cell and organ system …”