Organoids as preclinical models of human disease: progress and applications

Abstract

In the field of biomedical research, organoids represent a remarkable advancement that has the potential to revolutionize our approach to studying human diseases even before clinical trials. Organoids are essentially miniature 3D models of specific organs or tissues, enabling scientists to investigate the causes of diseases, test new drugs, and explore personalized medicine within a controlled laboratory setting. Over the past decade, organoid technology has made substantial progress, allowing researchers to create highly detailed environments that closely mimic the human body. These organoids can be generated from various sources, including pluripotent stem cells, specialized tissue cells, and tumor tissue cells. This versatility enables scientists to replicate a wide range of diseases affecting different organ systems, effectively creating disease replicas in a laboratory dish. This exciting capability has provided us with unprecedented insights into the progression of diseases and how we can develop improved treatments. In this paper, we will provide an overview of the progress made in utilizing organoids as preclinical models, aiding our understanding and providing a more effective approach to addressing various human diseases.

Keywords: drug screening; human disease; organoids; regenerative medicine; tumor.

Figure 1:

Timeline for the development of different types of organoids. Summary of research on critical landmarks in the establishment of various organoids. 3D, 3-dimensional; ASC, adult stem cells; hPSC, human pluripotent stem cells; mESC, embryonic stem cells.

Figure 2:

Multiple applications of organoid technology (by Figdraw). The schematic summarizes the different applications of organoids in many fields, including developmental biology, gene editing, drug screening, disease modeling, personalized therapy, and regenerative medicine.

Figure 3:

Liver organoids and brain organoids obtained from iPSCs and ESCs (by Figdraw). Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) respectively from the inner cell mass of blastocysts and somatic cell reprogramming through the cultivation of different numbers of days and cell factors to generate the corresponding organoids.

Figure 4:

Overview of organoid types (by Figdraw). Starting cell types include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), adult stem cells (ASCs), and tumor stem cells, which are aggregated into cell populations by self-organization. The cell population differentiates into three germ layers: endoderm, mesoderm, and ectoderm, which further specializes into various organoid types.