Traumatic brain injury (TBI) is a substantial cause of disability and death worldwide. Primary head trauma triggers chronic secondary injury mechanisms in the brain that are a focus of therapeutic efforts to treat TBI. Currently, there is no successful clinical strategy to repair brain injury. Cell transplantation therapies have demonstrated promise in attenuating secondary injury mechanisms of neuronal death and dysfunction in animal models of brain injury. In this study, we used a unilateral cortical contusion injury (CCI) model of sensorimotor brain injury to examine the effects of human induced pluripotent stem cell (hiPSC) transplantation on pathology in male and female adult mice. We determined transplanted hiPSC-derived neural stem cells (NSCs) and neuroblasts but not astrocytes best tolerate the injured host environment. Surviving NSC and neuroblast cells were clustered at the site of injection within the deep layers of the cortex and underlying corpus callosum. Cell grafts extended neuritic processes that crossed the midline into the contralateral corpus callosum or continued laterally within the external capsule to enter the ipsilateral entorhinal cortex. To determine the effect of transplantation on neuropathology, we performed sensorimotor behavior testing and stereological estimation of host neurons, astrocytes, and microglia within the contused cortex. These measures did not reveal a consistent effect of transplantation on recovery post-injury. Rather the positive and negative effects of cell transplantation were dependent on the host sex, highlighting the importance of developing patient-specific approaches to treat TBI. Our study underscores the complex interactions of sex, neuroimmune responses and cell therapy in a common experimental model of TBI.

创伤性脑损伤 (TBI) 是全世界残疾和死亡的重要原因。原发性头部外伤会触发大脑中的慢性继发性损伤机制，这是治疗 TBI 的重点。目前，还没有成功的临床策略来修复脑损伤。细胞移植疗法在减轻脑损伤动物模型中神经元死亡和功能障碍的继发性损伤机制方面已显示出前景。在这项研究中，我们使用感觉运动脑损伤的单侧皮质挫伤 (CCI) 模型来检查人类诱导多能干细胞 (hiPSC) 移植对雄性和雌性成年小鼠病理学的影响。我们确定移植的 hiPSC 衍生神经干细胞 (NSC) 和神经母细胞，但不是星形胶质细胞最能耐受受损的宿主环境。存活的 NSC 和成神经细胞聚集在皮层深层和下面胼胝体的注射部位。细胞移植物扩展神经炎突，穿过中线进入对侧胼胝体或在外囊内继续横向进入同侧内嗅皮层。为了确定移植对神经病理学的影响，我们对挫伤皮层内的宿主神经元、星形胶质细胞和小胶质细胞进行了感觉运动行为测试和体视评估。这些措施并未显示移植对损伤后恢复的一致影响。相反，细胞移植的正面和负面影响取决于宿主性别，突出了开发针对患者的 TBI 治疗方法的重要性。