Department of Immunology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Cells. 2021 Dec 30;11(1):108. doi: 10.3390/cells11010108.
The intrinsic capacity of human hematopoietic stem cells (hHSCs) to reconstitute myeloid and lymphoid lineages combined with their self-renewal capacity hold enormous promises for gene therapy as a viable treatment option for a number of immune-mediated diseases, most prominently for inborn errors of immunity (IEI). The current development of such therapies relies on disease models, both in vitro and in vivo, which allow the study of human pathophysiology in great detail. Here, we discuss the current challenges with regards to developmental origin, heterogeneity and the subsequent implications for disease modeling. We review models based on induced pluripotent stem cell technology and those relaying on use of adult hHSCs. We critically review the advantages and limitations of current models for IEI both in vitro and in vivo. We conclude that existing and future stem cell-based models are necessary tools for developing next generation therapies for IEI.
人类造血干细胞（hHSCs）的内在能力能够重建骨髓和淋巴谱系，加上其自我更新能力，为基因治疗作为许多免疫介导疾病的可行治疗选择提供了巨大的希望，尤其是对于先天免疫缺陷（IEI）。这种治疗方法的当前发展依赖于疾病模型，无论是体外还是体内，这些模型都可以详细研究人类的生理病理学。在这里，我们讨论了与发育起源、异质性以及随后对疾病建模的影响相关的当前挑战。我们回顾了基于诱导多能干细胞技术的模型和依赖于使用成人 hHSCs 的模型。我们批判性地回顾了现有的和未来的用于 IEI 的体外和体内模型的优缺点。我们得出结论，现有的和未来的基于干细胞的模型是为 IEI 开发下一代治疗方法的必要工具。
