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与外周血自然杀伤细胞(NK细胞)相比,从人脐带血来源的CD34干细胞体外分化而来的NK细胞在激活受体和细胞毒性活性方面更加平衡。

More balance toward activating receptors and cytotoxic activity of NK cells ex vivo differentiated from human umbilical cord blood-derived CD34 stem cells in comparison with peripheral blood NK cells.

作者信息

Ghaedrahmati Farhoodeh, Esmaeil Nafiseh, Akbari Vajihe, Ashrafi Farzaneh

机构信息

Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Heliyon. 2024 Aug 5;10(15):e35509. doi: 10.1016/j.heliyon.2024.e35509. eCollection 2024 Aug 15.

DOI:10.1016/j.heliyon.2024.e35509
PMID:39170467
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11336728/
Abstract

Adoptive immunotherapies that use functional NK cells depend on the availability of sufficient numbers of these cells. We expanded umbilical cord blood (UCB)-CD34 HSCs for 2 weeks and then differentiated them into NK cells and compared their function to peripheral blood (PB) NK cells. We assessed NKG2D, NKG2A, NKp30, NKp44, NKp46, and the expression of CD107a, CD57, CD69, FasL, PD-1, and IFN-γ level in two groups after co-culture with K562 cell line. We found that UCB-CD34-derived NK cells express significantly more NKG2D, NKp44, and NKp46 receptors than PB NK cells. PB NK cells expressed significantly higher NKG2A and CD57 than UCB-CD34-derived NK cells. In addition, UCB-CD34-derived NK cells significantly expressed CD107a more than PB NK cells. Based on our findings, UCB-CD34 cells can be a potentially advantageous source with strong cytotoxic function to produce allogeneic NK cells for adoptive cancer immunotherapy.

摘要

使用功能性自然杀伤(NK)细胞的过继性免疫疗法依赖于足够数量的此类细胞的可得性。我们将脐带血(UCB)-CD34造血干细胞扩增2周,然后将其分化为NK细胞,并将其功能与外周血(PB)NK细胞进行比较。在与K562细胞系共培养后,我们评估了两组中自然杀伤细胞激活受体NKG2D、抑制性受体NKG2A、自然杀伤细胞活化受体NKp30、NKp44、NKp46以及CD107a、CD57、CD69、FasL、程序性死亡受体1(PD-1)的表达和γ干扰素(IFN-γ)水平。我们发现,源自UCB-CD34的NK细胞比PB NK细胞表达显著更多的NKG2D、NKp44和NKp46受体。PB NK细胞比源自UCB-CD34的NK细胞表达显著更高水平的NKG2A和CD57。此外,源自UCB-CD34的NK细胞比PB NK细胞显著更多地表达CD107a。基于我们的研究结果,UCB-CD34细胞可能是一种具有强大细胞毒性功能的潜在优势来源,可用于生产用于过继性癌症免疫治疗的同种异体NK细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/c2f8987ef138/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/ecf9f968d6cc/gr4a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/c22dd2feab23/gr5a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/64eafec8100b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/b6ea43ee8020/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/c2f8987ef138/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/c826f55b8951/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/2a31224cf5cb/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/e76ed4946fe1/gr3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/ecf9f968d6cc/gr4a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/c22dd2feab23/gr5a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/64eafec8100b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/b6ea43ee8020/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc9/11336728/c2f8987ef138/gr8.jpg

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