Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.

由于梗死组织的永久性损失，中风通常会导致长期或终生残疾。尽管已经探索了多种干细胞移植通过增强神经可塑性来改善神经元缺陷行为，但是否可以重建梗死组织仍然未知。我们在这里培养了源自人类多能干细胞 (hPSC) 的人类大脑类器官，并将它们移植到遭受中风的 NOD-SCID 小鼠的梗塞核心和梗塞周围区域的交界处。几个月后，我们发现移植的类器官在梗塞核心存活良好，分化为靶神经元，修复梗塞组织，将轴突发送到远处的大脑靶点，并整合到宿主神经回路中，从而消除了中风小鼠的感觉运动缺陷行为，而从类器官移植解离的单细胞未能修复梗塞组织。我们的研究提供了一种通过类器官移植重建梗塞组织的新策略，从而逆转中风引起的残疾。