UPMC Stroke Institute, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.
Stroke. 2009 Feb;40(2):510-5. doi: 10.1161/STROKEAHA.108.526863. Epub 2008 Dec 18.
Investigators developing cellular therapy for stroke face many challenges. Preclinical models used for cellular therapy studies should be relevant to human stroke and predictive of benefit despite differences in stroke size, cerebrovascular anatomy, immune status, and neurological responses. Translating preclinical testing to human trials is compounded by consideration of delivery method and translation of dosing with cell survival. Many issues must be approached in designing clinical trials of cellular therapy for stroke, including appropriate outcome measures, controlling for confounding factors such as rehabilitation therapy, and possible surrogate outcomes using imaging such as MRI and newer imaging techniques. It is also important to establish standardized clinical protocols and clinical database registries in advance of early proof-of-concept studies. Investigators must adopt a standardized nomenclature and characterization schema for cell products to accurately define potency and determine clinical outcome from early proof-of-concept studies. The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.
致力于开发中风细胞疗法的研究人员面临诸多挑战。用于细胞疗法研究的临床前模型应与人类中风相关，并且尽管在中风大小、脑血管解剖结构、免疫状态和神经反应方面存在差异，但仍能预测疗效。将临床前测试转化为人体试验会因递送方法的考量以及细胞存活剂量的转化而变得更加复杂。在设计中风细胞疗法的临床试验时，必须解决许多问题，包括合适的结果指标、控制诸如康复治疗等混杂因素，以及使用MRI等成像技术和更新的成像技术可能得出的替代结果。在早期概念验证研究之前预先建立标准化的临床方案和临床数据库登记也很重要。研究人员必须为细胞产品采用标准化的命名法和表征方案，以便准确界定效力，并从早期概念验证研究中确定临床结果。组织了“干细胞疗法作为中风的新兴范例（STEPS）”会议，将临床和基础研究人员与行业及监管代表汇聚一堂，以评估该领域的关键问题，并创建一个指导未来研究的框架。
