斯坦福大学塞尔久·帕什卡（Sergiu Pasca）团队在跨物种器官移植领域取得突破性进展，相关成果发表于《自然》期刊。与传统将动物器官移植给人类以延续生命的异种移植不同，研究人员探索了反向移植路径：他们从人类皮肤干细胞中培育出微型三维脑类器官，并成功将其移植至经基因改造的幼鼠颅内。这项名为“异种皮层化”（xenocortication）的前沿技术，创造出了大脑皮层在生理结构上兼具人源与鼠源成分的嵌合体啮齿动物。

为了给人类神经元构建物理空间并实现生理融合，科学家利用基因工程技术精准抑制了小鼠大脑皮层和海马体绝大部分自身细胞的早期发育。在小鼠出生后的最初几天内，研究人员将特定的人类脑类器官植入其颅内所形成的空腔组织中。实验表明，移植的人类神经细胞不仅迅速融入宿主微环境并与小鼠外周神经系统建立功能性连接，而且严格遵循着人类神经发育的内在时间节律——即使在宿主小鼠步入成熟期后，这些人类神经元在最初几个月内依然保持着人类胎儿细胞的分子与生理特性。

这一嵌合体模型为攻克长期受制于伦理和实验限制的人类早期神经系统疾病提供了革命性的活体研究平台。在缺氧性脑瘫实验中，缺氧诱发了人类神经元的特异性损伤，而同处一脑的小鼠神经元则未受显著影响，成功再现了临床病理差异。此外，该技术有望应用于额颞叶痴呆、癫痫以及自闭症的病理机制解析与药物靶向筛选，打破过去在普通动物模型中屡遭临床失败的研发瓶颈。针对涉及人类神经组织的伦理关切，研究人员指出，小鼠颅腔极度有限的物理容积、人类与小鼠长达约7,000万年的演化鸿沟，以及显著的发育速度错配，在生物学层面上杜绝了高级人源认知意识在小鼠体内萌发的可能性。

Stanford University neuroscientist Sergiu Pasca and his research team have engineered a biological milestone in xenotransplantation, publishing details of mice possessing hybrid, partially human cerebral cortices in Nature. Departing from traditional cross-species procedures that transplant animal organs into human patients to sustain life, the researchers reversed the direction by transplanting human cellular material into animal hosts. Rather than utilizing intact organs, the team generated complex neural organoids derived from human skin-derived pluripotent stem cells, embedding them directly into murine cranial cavities to study living human neural circuitry.

The methodology, designated as “xenocortication,” relied on genetically modifying host mice to prevent their endogenous cerebral cortices and hippocampi from developing normally. Within the opening days of life following birth, human brain organoids were surgically grafted into the resulting neuroanatomical void, where they integrated organically with the host circulatory and nervous systems. Because transplanted neurons preserve their cell-intrinsic developmental clockwork rather than adapting to the rodent’s accelerated life cycle, the human brain cells continue exhibiting fetal properties across the initial months of the host mouse’s maturation, providing an unprecedented longitudinal window into human neurodevelopment.

This hybrid biological platform establishes transformative preclinical utility for investigating complex neuropathologies and screening pharmacological compounds. Initial trials focused on hypoxia-induced cerebral palsy demonstrated that oxygen deprivation selectively damaged human cortical neurons while leaving murine cells intact, replicating human vulnerability patterns that conventional animal models historically failed to capture. Researchers plan to deploy the models to interrogate frontotemporal dementia, epilepsy, and autism, bypassing translational drug screening failures. While grafting human neural substrates raises bioethical sensitivities, the authors emphasize that the 70m-year evolutionary divide separating primates from rodents, stark developmental asynchronous timings, and the minute volumetric capacity of the mouse cranium decisively preclude the emergence of higher human cognitive traits.

Source: Researchers have created a mouse with a partly human brai

Subtitle: It will help the development of drugs for neurological illnesses

Dateline: Sep 17th 2026\n