人多能干細胞再生NK細胞的側(cè)板中胚層細胞類器官系統(tǒng)

2023年2月，中國科學院動物研究所干細胞與再生研究所，干細胞與生殖生物學國家重點實驗室，中國科學院廣州生物醫(yī)藥與健康研究所，中國科學院再生生物學重點實驗室，（State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences,Beijing, China   CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou,Guangdong, China）Jinyong Wang 研究團隊在《Cell Discovery》上發(fā)表論文，標題為：“Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells ”

“人多能干細胞再生NK細胞的側(cè)板中胚層細胞類器官系統(tǒng)”

Abstract

Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a source of off-the-shelf cell products for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryoid body (EB) formation and feeder-based expansion steps, which are time-consuming and cause instability and high costs of manufacturing. Here, we develop an EB-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time-window of 27-day induction, millions of hPSC input can output over billions of iNK cells without the necessity of NK cell expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells via mechanisms of direct cytotoxicity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.

摘要

人多能干細胞(hPSC)誘導的NK (iNK)細胞是用于通用免疫治療的現(xiàn)成細胞產(chǎn)品的來源。利用人乳頭狀干細胞再生iNK細胞的傳統(tǒng)方法包括胚狀體(EB)的形成和基于喂食器的擴增步驟，這些步驟耗時且不穩(wěn)定，制造成本高。在這里，我們開發(fā)了一種無eb的類器官聚集方法，用于從hPSCs中再生NK細胞。在27天的短時間內(nèi)，數(shù)百萬個hPSC輸入可以輸出超過數(shù)十億個iNK細胞，而不需要NK細胞擴增器。iNK細胞高度表達經(jīng)典的毒性顆粒蛋白、凋亡誘導配體以及豐富的激活和抑制受體。在功能上，iNK細胞通過直接細胞毒性、細胞凋亡和抗體依賴的細胞毒性機制來根除人類腫瘤細胞。本研究為從人造血干細胞中再生人NK細胞提供了一種可靠的規(guī)模化方法，促進了NK細胞產(chǎn)品用于免疫治療的普遍可用性。

該論文中，從人ESC細胞系(hPSC-1, hPSC-2, hPSC-3, hPSC-4,和hPSC-5)培養(yǎng)是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯(lián)系北京締一生物400-166-8600.