小柯机器人

美国Sana生物技术公司Sonja Schrepfer团队近期取得重要工作进展，他们研究开发了低免疫诱导的多能干细胞，它们能在完全免疫能力的同种异体恒河猴体内长期存活。相关研究成果2023年5月8日在线发表于《自然—生物技术》杂志上。

据介绍，完全防止受体免疫系统排斥反应的异种基因细胞疗法的基因工程将取消对免疫抑制药物或封装的要求，并支持现成细胞产品的大规模生产。

此前，研究人员通过消耗HLA I类和II类分子并过表达CD47（B2M^−/−CIITA^−/−CD47⁺）来产生小鼠和人类低免疫多能干细胞（HIP）。为了确定这种策略在非人类灵长类动物中是否成功，研究人员设计了恒河猴HIP细胞，并移植到四只同种异体恒河猴中。HIP细胞在具有完全免疫活性的同种异体受体中存活了16周，并分化为几个谱系，而同种异体野生型细胞被强烈排斥。研究人员还将人类HIP细胞分化为具有内分泌活性的胰岛细胞，并表明它们在具有免疫活性的同种异体糖尿病人源化小鼠中存活了4周，并改善了糖尿病。HIP编辑的原代恒河猴胰岛在没有免疫抑制的异体恒河猴受体中存活了40周，而未经编辑的胰岛很快被排斥。

附：英文原文

Title: Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques

Author: Hu, Xiaomeng, White, Kathy, Olroyd, Ari G., DeJesus, Rowena, Dominguez, Antonia A., Dowdle, William E., Friera, Annabelle M., Young, Chi, Wells, Frank, Chu, Elaine Y., Ito, Cade Ellis, Krishnapura, Harini, Jain, Surbhi, Ankala, Ramya, McGill, Trevor J., Lin, August, Egenberger, Kyla, Gagnon, Allison, Michael Rukstalis, J., Hogrebe, Nathaniel J., Gattis, Corie, Basco, Ron, Millman, Jeffrey R., Kievit, Paul, Davis, Mark M., Lanier, Lewis L., Connolly, Andrew J., Deuse, Tobias, Schrepfer, Sonja

Issue&Volume: 2023-05-08

Abstract: Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient’s immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M/CIITA/CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected.

DOI: 10.1038/s41587-023-01784-x

Source: https://www.nature.com/articles/s41587-023-01784-x

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
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