Menzies Institute for Medical Research, School of Medicine, University of Tasmania, Hobart, TAS, Australia.
Menzies Institute for Medical Research, School of Medicine, University of Tasmania, Hobart, TAS, Australia; Centre for Eye Research Australia, The University of Melbourne, Melbourne, VIC, Australia; School of Medicine, University of Tasmania, Hobart, TAS, Australia.
Stem Cell Reports. 2023 Nov 14;18(11):2038-2046. doi: 10.1016/j.stemcr.2023.09.010. Epub 2023 Oct 12.
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold promise for transplantation medicine. Diverse human leukocyte antigen (HLA) profiles necessitate autologous cells or multiple cell lines for therapeutics, incurring time and cost. Advancements in CRISPR-Cas9 and cellular therapies have led to the conceptualization of "off-the-shelf" universal cell donor lines, free of immune rejection. Overcoming immune rejection is a challenge. This review outlines strategies to modulate the major histocompatibility complex (MHC) to generate a universal cell donor line. Upon bypassing MHC mismatch, multifaceted approaches are required to generate foreign host-tolerated cells. Universal cells harbor risks, namely immune escape and tumor formation. To mitigate, we review safety mechanisms enabling donor cell inactivation or removal. Achieving a universal cell line would reduce treatment wait time, eliminate donor search, and reduce graft-versus-host disease risk without immunosuppression. The pursuit of universally tolerated cells is under way, ready to transform transplantation and regenerative medicine.
人类胚胎干细胞 (ESCs) 和诱导多能干细胞 (iPSCs) 在移植医学方面具有广阔的应用前景。由于不同的人类白细胞抗原 (HLA) 谱需要使用自体细胞或多种细胞系进行治疗，因此这会耗费时间和成本。CRISPR-Cas9 和细胞疗法的进步促使人们产生了“现成的”通用细胞供体系的概念，这些细胞不会引起免疫排斥。克服免疫排斥是一个挑战。本综述概述了调节主要组织相容性复合体 (MHC) 以产生通用细胞供体系的策略。在绕过 MHC 不匹配后，需要采用多方面的方法来产生能够被外来宿主耐受的细胞。通用细胞存在免疫逃逸和肿瘤形成的风险。为了减轻这些风险，我们综述了使供体细胞失活或去除的安全机制。实现通用细胞系将减少治疗等待时间，消除供体搜索，并降低移植物抗宿主病风险，而无需免疫抑制。目前正在努力寻找普遍耐受的细胞，以推动移植和再生医学的发展。
