中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 1867-1874.doi: 10.4103/1673-5374.335689

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

用于再生疗法临床前测试的非人灵长类多能干细胞

  

  • 出版日期:2022-09-15 发布日期:2022-03-03

Non-human primate pluripotent stem cells for the preclinical testing of regenerative therapies

Ignacio Rodríguez-Polo1, 2, *, Rüdiger Behr1, 2, *   

  1. 1Research Platform Degenerative Diseases, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany; 2German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
  • Online:2022-09-15 Published:2022-03-03
  • Contact: Rüdiger Behr, Dr., rbehr@dpz.eu; Ignacio Rodríguez-Polo, Dr., IRodriguezPolo@dpz.eu.
  • Supported by:
    This work was partially supported by the German Centre for Cardiovascular Research (DZHK) and the German Primate Center – Leibniz Institute for Primate Research, which is financed by the Bundesrepublik Deutschland and the Bundesländer (Federal states) (Grant number 81Z0300201 to RB).

摘要: Neural Regen Res:非人灵长类多能干细胞用于细胞替代疗法临床前测试
    非人灵长类动物在基于多能干细胞的细胞替代疗法的临床前验证中发挥着关键作用。多能干细胞提高了受退行性疾病影响的组织和器官再生的可能性。在过去的 15 年中,按照临床标准获得人类诱导多能干细胞和胚胎干细胞系的方法得到了迅速发展。对于非人灵长类动物细胞替代疗法的临床前验证,有必要生成与人类对应物具有同源质量的非人灵长类多能干细胞。与人类细胞系统相比,多能干细胞技术在非人灵长类动物中的发展速度较慢。多能干细胞作为医疗产品的潜力彻底改变了再生医学。使用多能干细胞(重新)生成不同类型组织和器官的几种方法处于临床前开发的后期阶段。由于非人灵长类动物与人类的生理相似性,非人灵长类动物在专注于神经和心血管系统再生的研究中具有特殊的相关性。 
    来自德国灵长类动物中心—莱布尼茨灵长类动物研究所的Rüdiger Behr团队认为,非人灵长类动物为开发和验证基于多能干细胞的干预措施提供了独特的机会。与其他动物模型(例如小鼠)相比,非灵长类动物具有更长的寿命和更大的体型,可以进行长期的纵向研究来评估移植后的有效性和安全性。非人灵长类动物解剖学允许在几乎或没有适应的情况下使用成像技术、外科手术和诊所使用的设备。尽管只有少数研究比较了人类和非人灵长类动物-多能干细胞,但基因表达和支持条件方面的数据表明,细胞身份、行为和多能性的执行具有高度相似性。非人灵长类动物的研究也面临一些其他动物模型所没有的挑战,包括成本高、审批流程复杂,以及一些研究工具尚未完全开发用于该物种,例如基因组注释。有必要在非人灵长类动物中仔细规划和进行临床前研究,以提供研究的可临床转化性。
文章在《中国神经再生研究(英文版)》杂志2022年 9 月 9 期发表。
https://orcid.org/0000-0001-8816-6619 (Rüdiger Behr); https://orcid.org/0000-0003-1254-4972 (Ignacio Rodríguez-Polo)

Abstract: Non-human primates play a key role in the preclinical validation of pluripotent stem cell-based cell replacement therapies. Pluripotent stem cells used as advanced therapy medical products boost the possibility to regenerate tissues and organs affected by degenerative diseases. Therefore, the methods to derive human induced pluripotent stem cell and embryonic stem cell lines following clinical standards have quickly developed in the last 15 years. For the preclinical validation of cell replacement therapies in non-human primates, it is necessary to generate non-human primate pluripotent stem cell with a homologous quality to their human counterparts. However, pluripotent stem cell technologies have developed at a slower pace in non-human primates in comparison with human cell systems. In recent years, however, relevant progress has also been made with non-human primate pluripotent stem cells. This review provides a systematic overview of the progress and remaining challenges for the generation of non-human primate induced pluripotent stem cells/embryonic stem cells for the preclinical testing and validation of cell replacement therapies. We focus on the critical domains of (1) reprogramming and embryonic stem cell line derivation, (2) cell line maintenance and characterization and, (3) application of non-human primate pluripotent stem cells in the context of selected preclinical studies to treat cardiovascular and neurodegenerative disorders performed in non-human primates.

Key words: embryonic stem cells, induced pluripotent stem cells, non-human primates, pluripotent stem cells, preclinical, regeneration, reprogramming, translational research