Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, 77030, TX, USA,
Cell Mol Life Sci. 2014 Jul;71(14):2641-9. doi: 10.1007/s00018-014-1572-9. Epub 2014 Feb 8.
Since HIV/AIDS was first recognized in 1981, an urgent need has existed for the development of novel therapeutic strategies to treat the disease. Due to the current antiretroviral therapy not being curative, human stem cell-based therapeutic intervention has emerged as an approach for its treatment. Genetically modified hematopoietic stem cells (HSCs) possess the potential to self-renew, reconstitute the immune system with HIV-resistant cells, and thus control, or even eliminate, viral replication. However, HSCs may be difficult to isolate in sufficient number from HIV-infected individuals for transplantation and/or re-infusion of autologous HSCs preparations would also include some contaminating HIV-infected cells. Furthermore, since genetic modification of HSCs is not completely efficient, the risk of providing unprotected immune cells to become new targets for HIV to infect could contribute to continued immune system failure. Therefore, induced pluripotent stem cells (iPSCs) should be considered a new potential source of cells to be engineered for HIV resistance and subsequently differentiated into clonal anti-HIV HSCs or hematopoietic progeny for transplant. In this article, we provide an overview of the current possible cellular therapies for treating HIV/AIDS.
自 1981 年首次发现 HIV/AIDS 以来,人们迫切需要开发新的治疗策略来治疗这种疾病。由于目前的抗逆转录病毒疗法并非根治性的,因此基于人类干细胞的治疗干预已成为一种治疗方法。基因修饰的造血干细胞 (HSCs) 具有自我更新、用抗 HIV 细胞重建免疫系统的潜力,从而可以控制甚至消除病毒复制。然而,从 HIV 感染者中分离出足够数量的 HSCs 可能较为困难,而且自体 HSCs 制剂的再输注也会包含一些污染的 HIV 感染细胞。此外,由于 HSCs 的基因修饰并非完全有效,提供无保护的免疫细胞作为 HIV 感染的新靶标,可能会导致免疫系统持续衰竭。因此,诱导多能干细胞 (iPSCs) 应该被视为一种新的潜在细胞来源,可以对其进行工程改造以抵抗 HIV,随后分化为具有抗 HIV 能力的克隆性 HSCs 或造血祖细胞,用于移植。本文综述了目前用于治疗 HIV/AIDS 的可能的细胞疗法。