Department of Pathology, McGaw Medical Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Center for Transplantation Science, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA; Division of Transplantation, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Blood Rev. 2023 Sep;61:101113. doi: 10.1016/j.blre.2023.101113. Epub 2023 Jul 14.
Transfusion of allogeneic human red blood cell (hRBCs) is limited by supply and compatibility between individual donors and recipients. In situations where the blood supply is constrained or when no compatible RBCs are available, patients suffer. As a result, alternatives to hRBCs that complement existing RBC transfusion strategies are needed. Pig RBCs (pRBCs) could provide an alternative because of their abundant supply, and functional similarities to hRBCs. The ability to genetically modify pigs to limit pRBC immunogenicity and augment expression of human 'protective' proteins has provided major boosts to this research and opens up new therapeutic avenues. Although deletion of expression of xenoantigens has been achieved in genetically-engineered pigs, novel genetic methods are needed to introduce human 'protective' transgenes into pRBCs at the high levels required to prevent hemolysis and extend RBC survival in vivo. This review addresses recent progress and examines future prospects for clinical xenogeneic pRBC transfusion.
异体人红细胞(hRBC)的输注受到供体和受者个体之间的供应和相容性的限制。在血液供应受到限制或没有可用的相容 RBC 的情况下,患者会遭受痛苦。因此,需要替代 hRBC 的方法来补充现有的 RBC 输血策略。由于猪 RBC(pRBC)的供应丰富,并且与 hRBC 具有功能相似性,因此它们可能成为一种替代方法。通过基因修饰猪来限制 pRBC 的免疫原性并增强人“保护性”蛋白的表达的能力为这项研究提供了重大推动力,并开辟了新的治疗途径。尽管已经在基因工程猪中实现了异种抗原表达的缺失,但需要新的遗传方法将人“保护性”转基因导入 pRBC 中,以达到防止溶血和延长体内 RBC 存活所需的高水平。本文综述了最近的进展,并探讨了临床异种 pRBC 输注的未来前景。