Organoids 類器官– An Alternative to Lab Rats? 實驗老鼠的替代方案？ The Problems of Using Lab Rats People often jokingly say "you are a lab rat" when one is being experimented on something new. For decades, early stages of clinical trials use rodents like rats and mice before testing on human subjects. However, there are still two major issues around the use of animal models. First, the ethical dilemma: Does the benefit of drug testing outweigh the cost of animal suffering? Can we minimize the use of vertebrates in research? Second, the scientific dilemma: Can rats sufficiently represent human? Scientists have used rats and mice for modeling complex mammalian physiology and pathology. This is based on the notion that the making of the human body is instructed by a network of conserved proteins that are mostly found in rats and mice. Nevertheless, it remains challenging to accurately predict drug efficacy in animal models [1]. What if we can grow models of human organs, using real human cells instead? Organoids in a Nutshell Enter organoids, self-assembling, 3D miniature cell clusters that mimic aspects of the real organ. The word “organoid” has two parts: “Organ” refers to a collection of cells and tissues that work together to perform specific functions, while the suffix “-oid” means the resemblance of a specified object – in this case an organ. So … is an organoid just an organ, with the same geometry but just smaller? Not exactly. Organs, as you may know, have a characteristic shape and internal structures. For example, the small intestine is a tubular structure. However, an organoid of a small intestine does not look like winding tubes under a microscope. In fact, the small intestine organoid, which is the first organoid to be developed, appeared as spherical hollow sacs, with small bud-like protrusions on their surface. These buds mimic intestinal crypts, pockets that house stem cells in real intestines, though the overall structure bears no resemblance to the winding tube shape [2]. The Story of the First Organoid It is well known that the absorptive and secretory cells on the surface of our intestine are periodically replaced by new cells that are derived from stem cells. However, the exact identity of the stem cells remained elusive until 2007, when Hans Clevers' group made a pivotal advance [3]. They identified Lgr5, a marker unique to stem cells residing in crypts of small intestine. With these cells now identifiable and purifiable, it begs the question: Could they be grown outside the body? Toshiro Sato joined the lab as a postdoctoral fellow to answer precisely this question [2]. In the beginning of the study, Clevers and his team encountered a major problem – Intestinal stem cells would die when
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