Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.
Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.
复制标题
DOI：
10.3390/ijms18061190
复制
发表时间：
2017-06-03
影响因子：
5.6
通讯作者：
Rohde E
中科院分区：
文献类型：
--
作者：
Gimona M;Pachler K;Laner-Plamberger S;Schallmoser K;Rohde E
来源于干细胞和祖细胞的细胞外囊泡（EV）可以具有与其亲本细胞相当的治疗效果，并且被认为是用于治疗多种疾病的有前景的药剂。为此，必须设计策略，以成功地转化EV研究，并开发安全有效的治疗方法，同时考虑到适用的法规。在这里，我们讨论了电动汽车从实验室到患者的沿着生产、安全性和有效性测试的要求。EV治疗的发展受到源细胞类型和靶疾病的影响。在这篇文章中，我们表达了我们的观点，基于我们在制造生物治疗剂用于常规使用或临床测试的经验，并专注于推进间充质基质细胞（MSC）衍生的EV治疗的策略。我们还讨论了在未满足临床需求的选定疾病（如临界尺寸骨缺损、大疱性表皮和脊髓损伤）中测试MSC-EV的基本原理。虽然科学界，制药公司和临床医生正在进入临床试验，以测试各种基于EV的产品的治疗潜力，但确定每种治疗方法中建议的效力的作用模式仍然是转化路径的主要挑战。
Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.