Ji Xiao-Li, Ma Ling, Zhou Wen-Hao, Xiong Man
Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
Transl Pediatr. 2021 Feb;10(2):435-445. doi: 10.21037/tp-20-262.
Ischemic brain injury is a common cause of long-term neurological deficits in children as well as adults, and no efficient treatments could reverse the sequelae in clinic till now. Stem cells have the capacity of self-renewal and multilineage differentiation. The therapeutic efficacy of stem cell transplantation for ischemic brain injury have been tested for many years. The grafts could survive and mature in the ischemic brain environment. Stem cell transplantation could improve functional recovery of ischemic brain injury models in pre-clinical trials. The potential mechanisms included cell replacement, release of neurotrophic and anti-inflammatory factors, immunoregulation as well as activation of endogenous neurogenesis. Besides, many clinical trials were conducted and some of trials already had preliminary results. From the current published data, cell transplantation for clinical application is safe and feasible. No severe adverse events and tumorigenesis were reported. While the therapeutic efficacy of stem cell therapy in clinic still needs more evidences. In this review, we overviewed the studies about stem cell therapy for ischemic brain injury. Different types of stem cells used for transplantation as well as the therapeutic mechanisms were discussed in detail. The related pre-clinical and clinical trials were summarized into two separate tables. In addition, we also discussed the unsolved problems and concerns about stem cell therapy for ischemic brain injury that need to be overcome before clinic transformation.
缺血性脑损伤是儿童和成人长期神经功能缺损的常见原因,迄今为止临床上尚无有效的治疗方法能够逆转后遗症。干细胞具有自我更新和多向分化的能力。干细胞移植治疗缺血性脑损伤的疗效已得到多年验证。移植的干细胞能够在缺血性脑环境中存活并成熟。在临床前试验中,干细胞移植可改善缺血性脑损伤模型的功能恢复。其潜在机制包括细胞替代、释放神经营养因子和抗炎因子、免疫调节以及激活内源性神经发生。此外,已经开展了许多临床试验,其中一些试验已经取得了初步结果。从目前已发表的数据来看,临床应用细胞移植是安全可行的。未报告严重不良事件和肿瘤发生情况。然而,干细胞治疗在临床上的疗效仍需要更多证据。在本综述中,我们概述了关于干细胞治疗缺血性脑损伤的研究。详细讨论了用于移植的不同类型干细胞及其治疗机制。相关的临床前和临床试验总结在两个单独的表格中。此外,我们还讨论了缺血性脑损伤干细胞治疗在临床转化之前需要克服的未解决问题和担忧。