By Ian Cheng 鄭朗健 3 separated from the other cells in the intestine. Sato tried thousands of combinations of growth factors to arrive at the conditions suitable for "eternal growth." They used a cocktail of three growth factors: R-spondin, epidermal growth factor, and noggin [4]. Instead of working on a 2D surface, they used a soft, porous material called Matrigel, which provides the stem cells with a 3D space to grow, just like inside of the body [5]. The results were shocking. "[Toshiro] realized what he had created was not just a lump of stem cells. It was a structure that recapitulates the normal structure of a gut and contains all the cell types of the epithelium, and even the cell types would be in the right location," Dr. Clevers recalled [2]. The stem cells did not simply multiply; they differentiated into multiple cell types and selforganized into unique spheroid structures. Sato and Clevers were not the first to use the term "organoid." It had been applied without consistent definitions to various 3D cultures since mid-1960s. But their 2009 breakthrough launched a field explosion: Stomach, colon, liver, and pancreas organoids were created using the same principles – planting stem cells on a 3D culture supplemented with growth factors between 2010 and 2013 [5, 6]. This rapid expansion created a need for clarity. In 2014, Lancaster and Knoblich formally defined an organoid as "a collection of organ-specific cell types that develops from stem cells or organ progenitors and self-organizes through cell sorting and spatially restricted lineage commitment" – a definition that captured what Sato, Clevers and their colleagues had accidentally discovered five years earlier [5]. Why Do We Need Organoids? In 2013, the Clevers and Watanabe labs published another pivotal research paper. They showed that intestine organoids transplanted to an injured area of the mice intestine could function normally [7]. The transplanted organoids integrated so well that they were indistinguishable from the host tissue when examined under the microscope [2]. The discovery opened a window for scientists to ponder the possibility of organoids in regenerative medicine. Patient-derived organoids enable autologous transplantation – transplanting one’s own tissues back to the body to replace the function of failing organs – solving the host-versus-graft problem in transplantation (the patient’s immune system attacks the transplanted organ from donor). In 2024, a group of researchers transplanted patient-derived organoids of pancreas (islets) into a patient with type I diabetes. Seventy-five days after the transplantation, the patient achieved insulin independence [8], in a disease which is otherwise lifelong, highlighting the potential of organoids in autologous transplantation. The success in this single patient warrants further clinical studies. Beyond regenerative medicines, researchers use animal models traditionally as an analogy to humans, and it has indeed provided us with ample insights about treating diseases. Yet there are features specific to humans that we cannot model with animal models like rats and mice [9]. Organoids derived from humans can act as a window to these features. A prime example is using organoids to understand the human brain – arguably the most complex object in the universe. Brain organoids are a simplified version of the brain,
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