Ondriš Juraj, Schwamborn Jens Christian, Olcese Umberto
Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, Amsterdam, 1098 XH, The Netherlands.
University of Luxembourg, Campus 6, Avenue du Swing L-4367, Belvaux, Luxembourg.
Cell Mol Life Sci. 2025 Jun 9;82(1):227. doi: 10.1007/s00018-025-05767-w.
The lack of effective therapeutic options for patients suffering from neurological impairments related to acquired brain damage requires novel translational strategies, among which transplantation of neural tissue is receiving strong attention. One of the most recent developments involves the implantation of brain organoid models, derived from embryonic or induced pluripotent stem cells, into damaged rodent cortices. While this approach is gaining popularity, the extent of graft integration within the host tissue remains poorly understood. This review aims to examine whether xenotransplanting organoids into cortical tissue induces functional recovery and plastic adaptation to the damaged implantation sites. Physiological indications of grafted organoid plasticity and integration into the host included viability, corticogenesis, vascularisation, growth, and the development of area-specific morphological identities. The functional integration into host neural circuitry has been probed by tracing of axonal projection growth according to implantation sites, but also through observations of spontaneous, stimulus evoked, and selectively tuned activity of grafted neurons. Finally, some studies also investigated whether the engraftment procedure facilitated behavioural recovery in tasks requiring motor, memory, or reward-seeking functions. Overall, organoid grafts show signs of progressive anatomical, functional, and behaviourally-relevant integration within the damaged host cortices. Yet, further investigation is necessary before this transplantation approach can be actually translated into a robust method to achieve functional restoration in patients suffering from brain damage.
对于患有与后天性脑损伤相关的神经功能障碍的患者而言，缺乏有效的治疗选择需要新的转化策略，其中神经组织移植受到了广泛关注。最近的进展之一是将源自胚胎或诱导多能干细胞的脑类器官模型植入受损的啮齿动物皮质中。虽然这种方法越来越受欢迎，但移植组织在宿主组织中的整合程度仍知之甚少。本综述旨在研究将类器官异种移植到皮质组织中是否能诱导功能恢复以及对受损植入部位的可塑性适应。移植类器官可塑性及整合入宿主的生理指标包括活力、皮质发生、血管生成、生长以及特定区域形态特征的发育。通过根据植入部位追踪轴突投射生长，以及观察移植神经元的自发活动、刺激诱发活动和选择性调节活动，来探究其在宿主神经回路中的功能整合。最后，一些研究还调查了移植过程是否有助于在需要运动、记忆或奖赏寻求功能的任务中实现行为恢复。总体而言，类器官移植在受损宿主皮质中显示出逐步的解剖学、功能和行为相关整合的迹象。然而，在这种移植方法能够真正转化为一种在脑损伤患者中实现功能恢复的可靠方法之前，还需要进一步研究。
