Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL 33612, USA.
KM Pharmaceutical Consulting LLC, Washington, DC 20006, USA.
Int J Mol Sci. 2020 Apr 19;21(8):2845. doi: 10.3390/ijms21082845.
Human mesenchymal stem cells have been explored for their application in cell-based therapies targeting stroke. Identifying cell lines that stand as safe, accessible, and effective for transplantation, while optimizing dosage, timing, and method of delivery remain critical translational steps towards clinical trials. Preclinical studies using bone marrow-derived NCS-01 cells show the cells' ability to confer functional recovery in ischemic stroke. Coculturing primary rat cortical cells or human neural progenitor cells with NCS-01 cells protects against oxygen-glucose deprivation. In the rodent middle cerebral artery occlusion model, intracarotid artery administration of NCS-01 cells demonstrate greater efficacy than other mesenchymal stem cells (MSCs) at improving motor and neurological function, as well as reducing infarct volume and peri-infarct cell loss. NCS-01 cells secrete therapeutic factors, including basic fibroblast growth factor and interleukin-6, while also demonstrating a potentially novel mechanism of extending filopodia towards the site of injury. In this review, we discuss recent preclinical advancements using in vitro and in vivo ischemia models that support the transplantation of NCS-01 in human stroke trials. These results, coupled with the recommendations put forth by the consortium of Stem cell Therapeutics as an Emerging Paradigm for Stroke (STEPS), highlight a framework for conducting preclinical research with the ultimate goal of initiating clinical trials.
人类间充质干细胞已被探索用于针对中风的基于细胞的治疗。确定安全、可及和有效的细胞系，同时优化剂量、时间和递送方法，仍然是向临床试验转化的关键步骤。使用骨髓来源的 NCS-01 细胞进行的临床前研究表明，这些细胞具有在缺血性中风中赋予功能恢复的能力。将原代大鼠皮质细胞或人神经祖细胞与 NCS-01 细胞共培养可防止氧葡萄糖剥夺。在啮齿动物大脑中动脉闭塞模型中，NCS-01 细胞经颈动脉内给药，在改善运动和神经功能、减少梗死体积和梗死周围细胞丢失方面，比其他间充质干细胞 (MSCs) 更有效。NCS-01 细胞分泌治疗因子，包括碱性成纤维细胞生长因子和白细胞介素 6，同时还表现出一种潜在的新型延伸丝状伪足向损伤部位的机制。在这篇综述中，我们讨论了最近使用体外和体内缺血模型的临床前进展，这些进展支持将 NCS-01 移植到人类中风试验中。这些结果，加上干细胞治疗新兴范式治疗中风联盟 (STEPS) 提出的建议，突出了一个进行临床前研究的框架，最终目标是启动临床试验。
