Organoids: A historical perspective of thinking in three dimensions

Abstract

In the last ten years, there has been a dramatic surge in the number of publications where single or groups of cells are grown in substrata that have elements of basement membrane leading to the formation of tissue-like structures referred to as organoids. However, this field of research began many decades ago, when the pioneers of cell culture began to ask questions we still ask today: How does organogenesis occur? How do signals integrate to make such vastly different tissues and organs given that the sequence of the genome in our trillions of cells is identical? Here, we summarize how work over the past century generated the conceptual framework that has allowed us to make progress in the understanding of tissue-specific morphogenetic programs. The development of cell culture systems that provide accurate and physiologically relevant models are proving to be key in establishing appropriate platforms for the development of new therapeutic strategies.

Figure 1.

Number of publications per year on organoids and 3D cell cultures according to PubMed. The number of publications per year is graphed for the following PubMed searches: “organoids [tw]” is shown in red squares, “organoid [tw]” is shown in blue circles, and “3D cell culture” is shown in green triangles. Figure courtesy of Neil Smith.

Figure 2.

Timeline of techniques and experiments leading to the current organoid field. The images shown in the 1975–1977 box are from Lyon et al. (2015), and are displayed under the terms of a Creative Commons License. Figure courtesy of Neil Smith.