Boltze Johannes, Arnold Antje, Walczak Piotr, Jolkkonen Jukka, Cui Lili, Wagner Daniel-Christoph
Department of Cell Therapy, Fraunhofer-Institute for Cell Therapy and Immunology , Leipzig , Germany ; Translational Center for Regenerative Medicine, University of Leipzig , Leipzig , Germany.
Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, MD , USA ; Institute for Cell Engineering, Johns Hopkins University , Baltimore, MD , USA.
Front Neurol. 2015 Jul 20;6:155. doi: 10.3389/fneur.2015.00155. eCollection 2015.
Cell therapies are increasingly recognized as a promising option to augment the limited therapeutic arsenal available to fight ischemic stroke. During the last two decades, cumulating preclinical evidence has indicated a substantial efficacy for most cell treatment paradigms and first clinical trials are currently underway to assess safety and feasibility in patients. However, the strong and still unmet demand for novel stroke treatment options and exciting findings reported from experimental studies may have drawn our attention away from potential side effects related to cell therapies and the ways by which they are commonly applied. This review summarizes common and less frequent adverse events that have been discovered in preclinical and clinical investigations assessing cell therapies for stroke. Such adverse events range from immunological and neoplastic complications over seizures to cell clotting and cell-induced embolism. It also describes potential complications of clinically applicable administration procedures, detrimental interactions between therapeutic cells, and the pathophysiological environment that they are placed into, as well as problems related to cell manufacturing. Virtually each therapeutic intervention comes at a certain risk for complications. Side effects do therefore not generally compromise the value of cell treatments for stroke, but underestimating such complications might severely limit therapeutic safety and efficacy of cell treatment protocols currently under development. On the other hand, a better understanding will provide opportunities to further improve existing therapeutic strategies and might help to define those circumstances, under which an optimal effect can be realized. Hence, the review eventually discusses strategies and recommendations allowing us to prevent or at least balance potential complications in order to ensure the maximum therapeutic benefit at minimum risk for stroke patients.
细胞疗法越来越被认为是一种有前景的选择，可扩充用于对抗缺血性中风的有限治疗手段。在过去二十年中，越来越多的临床前证据表明，大多数细胞治疗模式都具有显著疗效，目前正在进行首批临床试验以评估其在患者中的安全性和可行性。然而，对新型中风治疗方案的强烈且仍未满足的需求，以及实验研究报告的令人兴奋的发现，可能使我们的注意力从与细胞疗法及其常用应用方式相关的潜在副作用上转移开了。本综述总结了在评估中风细胞疗法的临床前和临床研究中发现的常见和较少见的不良事件。这些不良事件包括从免疫和肿瘤并发症到癫痫发作，再到细胞凝血和细胞诱导的栓塞等。它还描述了临床适用给药程序的潜在并发症、治疗细胞之间的有害相互作用以及它们所处的病理生理环境，以及与细胞制造相关的问题。实际上，每种治疗干预都存在一定的并发症风险。因此，副作用通常不会损害细胞疗法对中风的治疗价值，但低估此类并发症可能会严重限制目前正在开发的细胞治疗方案的治疗安全性和疗效。另一方面，更好地理解将提供机会进一步改进现有的治疗策略，并可能有助于确定在哪些情况下可以实现最佳效果。因此，本综述最终讨论了一些策略和建议，使我们能够预防或至少平衡潜在并发症，以确保中风患者在最小风险下获得最大治疗益处。
