Advances in removing mass transport limitations for more physiologically relevant in vitro 3D cell constructs

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Spheroids and organoids are promising models for biomedical applications ranging from human disease modeling to drug discovery. A main goal of these 3D cell-based platforms is to recapitulate important physiological parameters of their in vivo organ counterparts. One way to achieve improved biomimetic architectures and functions is to culture cells at higher density and larger total numbers. However, poor nutrient and waste transport lead to low stability, survival, and functionality over extended periods of time, presenting outstanding challenges in this field. Fortunately, important improvements in culture strategies have enhanced the survival and function of cells within engineered microtissues/organs. Here, we first discuss the challenges of growing large spheroids/organoids with a focus on mass transport limitations, then highlight recent tools and methodologies that are available for producing and sustaining functional 3D in vitro models. This information points toward the fact that there is a critical need for the continued development of novel cell culture strategies that address mass transport in a physiologically relevant human setting to generate long-lasting and large-sized spheroids/organoids.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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