Space lab inspired generation of a human iPSC-derived organ capable of immediate blood perfusion

Human induced pluripotent stem cell (hiPSC)-derived organoids are promising alternatives for organ transplant to address donor organ shortages. However, post-transplantation impediment without immediate blood perfusion arises owing to the absence of large blood vessels (BVs) suitable for anastomosis. We developed a space lab experiment-inspired culture technique to incorporate a large BV into hiPSC-liver organoids (LOs) by facilitating tissue fusion. We demonstrated that microgravity conditions affected cell growth and metabolism of hiPSC-LOs. Upon perfusion culture through the large BV, the hiPSC-LO responds to shear stress, resulting in augmented tissue size and enhanced metabolic functions. Finally, individual large BV-equipped hiPSC-LOs were transplanted to the femoral artery of immunodeficient rats via vascular anastomosis, where they functioned for 1 week. Taken together, we have successfully generated hiPSC-derived organs amenable to vascular anastomosis, with potential implications for future organ transplantation endeavors.