Our understanding of the biology of the intestinal epithelium has advanced since the establishment of an organoid culture system. Although organoids have enabled investigation of the mechanism of self-renewal of human intestinal stem cells in vitro, it remains difficult to clarify the behavior of human normal and diseased intestinal epithelium in vivo. Recently, we developed a xenotransplantation system in which human intestinal organoids are engrafted onto epithelium-depleted mouse colons. This xenograft recapitulated the original tissue structures. Upon xenotransplantation, normal colon organoids developed normal colon crypt structures without tumorigenesis, whereas tumor-derived organoids formed colonic tumors resembling the original tumors. The non-tumorigenicity of human intestinal organoids highlights the safety of organoid-based regenerative medicine. As an example of regenerative medicine for short bowel syndrome, we devised a unique organ-repurposing approach to convert colons into small intestines by organoid transplantation. In this approach, the transplanted rat small intestinal organoids not only engrafted onto the rat colons but also remodeled the colon subepithelial structures into a small intestine-like conformation. Luminal flow accelerated the maturation of villi in the small intestine, which promoted the formation of a lymphovascular network mimicking lacteals. In this review, we provide an overview of recent advances in gastrointestinal organoid transplantation and share our understanding of human disease biology and regenerative medicine derived from these studies.

Because recovery from upper limb paralysis after stroke is challenging, compensatory approaches have been the main focus of upper limb rehabilitation. However, based on fundamental and clinical research indicating that the brain has a far greater potential for plastic change than previously thought, functional restorative approaches have become increasingly common. Among such interventions, constraint-induced movement therapy, task-specific training, robotic therapy, neuromuscular electrical stimulation (NMES), mental practice, mirror therapy, and bilateral arm training are recommended in recently published stroke guidelines. For severe upper limb paralysis, however, no effective therapy has yet been established. Against this background, there is growing interest in applying brain–machine interface (BMI) technologies to upper limb rehabilitation. Increasing numbers of randomized controlled trials have demonstrated the effectiveness of BMI neurorehabilitation, and several meta-analyses have shown medium to large effect sizes with BMI therapy. Subgroup analyses indicate higher intervention effects in the subacute group than the chronic group, when using movement attempts as the BMI-training trigger task rather than using motor imagery, and using NMES as the external device compared with using other devices. The Keio BMI team has developed an electroencephalography-based neurorehabilitation system and has published clinical and basic studies demonstrating its effectiveness and neurophysiological mechanisms. For its wider clinical application, the positioning of BMI therapy in upper limb rehabilitation needs to be clarified, BMI needs to be commercialized as an easy-to-use and cost-effective medical device, and training systems for rehabilitation professionals need to be developed. A technological breakthrough enabling selective modulation of neural circuits is also needed.