利用功能化水凝胶包封扁桃体来源的淋巴内皮细胞增强CD8+ T细胞的体外活性。

IF 12.4 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Theranostics Pub Date : 2025-01-01 DOI:10.7150/thno.100079
Heesun Hong, Chan Hum Park, Ji Seung Lee, Kyunghee Kim, Sudarshini Nath, Moon Sik Oh, Sol Kim, Chul Hee Lee, Ki Hyun Kim, Woo Hee Choi, Kyu Young Choi, Hae Sang Park, Ok Joo Lee, In-Sun Hong, Soon Hee Kim
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引用次数: 0

摘要

基本原理:本研究探讨了一种利用基于生物材料的系统对免疫细胞进行编程的方法,为传统的离体细胞操作技术提供了一种替代方法。它通过引入明胶-透明质酸(GH-GMA)水凝胶系统,解决了工程过继T细胞疗法的局限性,例如T细胞衰竭。方法:我们对扁桃体间充质干细胞(TMSCs)、淋巴内皮细胞(T- lecs)、刺激T- cd8 + T细胞(STCs)和GH-GMA生物材料进行了表征。10% 5:1 GH-GMA水凝胶,负载抗cd28,细胞因子白介素-2 (IL-2)和血管内皮生长因子C (VEGF-C),形成能够释放这些免疫刺激因子的功能性水凝胶。来源于扁桃体间充质干细胞(TMSCs)的T- lec球体被包裹在水凝胶中,作为T细胞的抗原提呈细胞。结果:STCs和T-LEC球体在功能水凝胶中共包封,培养过程中STCs显著扩增和富集。此外,当癌细胞与STCs和T-LECs共包被时,STCs向癌细胞的迁移增加,癌细胞上PD-L1的表达升高。结论:这些研究结果表明,GH-GMA水凝胶与抗cd28、IL-2、VEGF-C和T- lec球体联合可增强T细胞活性,为癌症免疫治疗和调节抑制性肿瘤微环境提供了一个有希望的平台。
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Ex vivo enhancement of CD8+ T cell activity using functionalized hydrogel encapsulating tonsil-derived lymphatic endothelial cells.

Rationale: This study investigates a method for programming immune cells using a biomaterial-based system, providing an alternative to traditional ex vivo cell manipulation techniques. It addresses the limitations of engineered adoptive T cell therapies, such as T cell exhaustion, by introducing a gelatin-hyaluronic acid (GH-GMA) hydrogel system. Methods: We characterized tonsil mesenchymal stem cells (TMSCs), lymphatic endothelial cells (T-LECs), stimulated T-CD8+ T cells (STCs), and GH-GMA biomaterials. The 10% 5:1 GH-GMA hydrogel, loaded with anti-CD28, cytokines interleukin-2 (IL-2) and vascular endothelial growth factor C (VEGF-C), forms a functional hydrogel capable of releasing these immune-stimulating factors. T-LEC spheroids, derived from tonsil mesenchymal stem cells (TMSCs), were encapsulated within the hydrogel to act as antigen-presenting cells for T cells. Results: Co-encapsulation of STCs and T-LEC spheroids in the functional hydrogel resulted in significant expansion and enrichment of STCs during cultivation. Moreover, when cancer cells were co-encapsulated with STCs and T-LECs, there was increased migration of STCs towards the cancer cells and elevated expression of PD-L1 on the cancer cells. Conclusions: These findings suggest that the GH-GMA hydrogel, combined with anti-CD28, IL-2, VEGF-C, and T-LEC spheroids, enhances T cell activity, presenting a promising platform for cancer immunotherapies and modulation of the suppressive tumor microenvironment.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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