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Correction to “Activation of NR1H3 attenuates the severity of septic myocardial injury by inhibiting NLRP3 inflammasome” 对 "通过抑制 NLRP3 炎症小体激活 NR1H3 减轻脓毒症心肌损伤的严重程度 "的更正
IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-15 DOI: 10.1002/btm2.10707

Chao Deng, Qiong Liu, Huadong Zhao, Lu Qian, Wagnrui Lei, Wenwen Yang, Zhenxing Liang, Ye Tian, Shaofei Zhang, Changyu Wang, Ying Chen, Yang Yang. Activation of NR1H3 attenuates the severity of septic myocardial injury by inhibiting NLRP3 inflammasome. Bioeng Transl Med. 2023; 8(3):e10517.

An inaccuracy has been found in the statistical graph of ABCA1 in Figure 2c of the published article. The corrected version of Figure 2 is shown below.

We apologize for this error.

邓超、刘琼、赵华东、钱璐、雷万瑞、杨雯雯、梁振兴、田野、张少飞、王长宇、陈颖、杨洋 通过抑制NLRP3炎性体激活NR1H3减轻脓毒症心肌损伤的严重程度Bioeng Transl Med. 2023;8(3):e10517.在已发表文章的图 2c 中发现 ABCA1 的统计图表有误。我们对这一错误表示歉意。
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引用次数: 0
MHCI trafficking signal‐based mRNA vaccines strengthening immune protection against RNA viruses 基于 MHCI 转运信号的 mRNA 疫苗可加强对 RNA 病毒的免疫保护
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-15 DOI: 10.1002/btm2.10709
Yupei Zhang, Songhui Zhai, Shugang Qin, Yuting Chen, Kepan Chen, Zhiying Huang, Xing Lan, Yaoyao Luo, Guohong Li, Hao Li, Xi He, Meiwan Chen, Zhongwei Zhang, Xingchen Peng, Xin Jiang, Hai Huang, Xiangrong Song
The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD‐based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD‐based mRNA vaccines encoding binding receptor‐binding domain (RBD) of SARS‐CoV‐2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.
主要组织相容性复合体 I 类(MHCI)贩运信号(MITD)在提高 mRNA 疫苗的功效方面发挥着关键作用。然而,目前还缺乏对其在增强 RNA 病毒感染免疫反应方面功效的研究。在此,我们开发了一种创新的 mRNA 疫苗配方策略。这种方法是将 MITD 整合到编码病毒抗原的 mRNA 序列中。从机理上讲,基于 MITD 的 mRNA 疫苗可以通过模仿 MHCI 分子的动态贩运特性来加强免疫保护,从而扩大记忆特异性 B 细胞和 T 细胞。基于 MITD 的 mRNA 疫苗模型编码了 SARS-CoV-2 的结合受体结合域 (RBD),其保护持续时间长、储存稳定性最佳、效力广泛且安全性高。
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引用次数: 0
Activated neutrophils: A next generation cellular immunotherapy 活化的中性粒细胞新一代细胞免疫疗法
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-13 DOI: 10.1002/btm2.10704
Ninad Kumbhojkar, Samir Mitragotri
Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype. Activation brings about significant changes to neutrophil biology such as increased lifespan, inflammatory cytokine secretion, and enhanced effector functions. Activated neutrophils also possess the potential to stimulate the downstream immune response and are described as essential effectors in the immune response to tumors. This makes activated neutrophils an interesting candidate for cell therapies. Here, we review the biology of activated neutrophils in detail. We discuss the different ways neutrophils can be activated and the effect they have on other immune cells for stimulation of downstream immune response. We review the conditions where activated neutrophil therapy can be therapeutically beneficial and discuss the challenges associated with their eventual translation. Overall, this review summarizes the current state of understanding of neutrophil‐based immunotherapies and their clinical potential.
细胞疗法是新型疗法的前沿。尽管中性粒细胞是人体血液循环中数量最多的免疫细胞,但由于其寿命短,而且人们对其在各种疾病的病理生理学中的作用了解甚少,因此中性粒细胞并不被认为是细胞疗法的可行选择。在炎症情况下,中性粒细胞表现出活化表型。活化会使中性粒细胞的生物学特性发生重大变化,如寿命延长、分泌炎症细胞因子和增强效应功能。活化的嗜中性粒细胞还具有刺激下游免疫反应的潜能,并被描述为肿瘤免疫反应的基本效应器。这使得活化的中性粒细胞成为细胞疗法的有趣候选者。在此,我们将详细回顾活化中性粒细胞的生物学特性。我们讨论了活化中性粒细胞的不同方式及其对其他免疫细胞刺激下游免疫反应的影响。我们回顾了活化中性粒细胞疗法对治疗有益的条件,并讨论了与最终转化相关的挑战。总之,这篇综述总结了目前对基于中性粒细胞的免疫疗法及其临床潜力的理解。
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引用次数: 0
Immunotherapy against glioblastoma using backpack‐activated neutrophils 利用背包激活的中性粒细胞对胶质母细胞瘤进行免疫治疗
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-13 DOI: 10.1002/btm2.10712
Tatsuya Fukuta, Ninad Kumbhojkar, Supriya Prakash, Suyog Shaha, A. Da Silva‐Candal, Kyung Soo Park, Samir Mitragotri
Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug‐free disk‐shaped backpacks, termed Cyto‐Adhesive Micro‐Patches (CAMPs) for treating GBM. CAMP‐adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti‐PD1 antibody (aPD‐1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD‐1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice‐bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD‐1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD‐1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.
免疫检查点抑制剂(ICIs)是治疗多形性胶质母细胞瘤(GBM)的新候选疗法;然而,由于局部和全身免疫抑制环境的影响,ICIs 的临床疗效有限。因此,刺激局部和全身免疫环境的治疗方法可以提高 ICIs 的疗效。在此,我们报告了一种采用中性粒细胞(NE)的收养细胞疗法,这种疗法通过表面附着无药物的圆盘状背包(称为细胞粘附微补丁(CAMPs))来激活中性粒细胞,用于治疗 GBM。粘附了 CAMP 的中性粒细胞(NE/CAMPs)能显著提高抗 PD1 抗体(aPD-1)在皮下小鼠 GBM 模型(GL261)中的疗效。NE/CAMPs和aPD-1的组合能完全消退小鼠皮下GL261肿瘤。此外,还在正位 GL261 模型中测试了 NE/CAMPs 对 GBM 的疗效。中性粒细胞迁移到脑内的能力不受 CAMP 附着的影响,而且在携带正位 GBM 的小鼠中观察到脑内 NE/CAMP 的聚集。NE/CAMPs和aPD-1的联合治疗激活了由T细胞介导的全身免疫反应,与单用aPD-1相比,在正位GBM模型中显示出更好的治疗反应。这些结果表明,NE/CAMPs 的免疫调节作用为结合 ICIs 治疗 GBM 提供了一种潜在的方法。
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引用次数: 0
Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift 富含 IL-10 modRNA 的人脂肪衍生多能基质细胞可改善糖尿病伤口愈合:触发巨噬细胞表型转变
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-07 DOI: 10.1002/btm2.10711
Yuxin Zhang, Wei Wang, Liang Chen, Heng Wang, Dong Dong, Jingjing Zhu, Yu Guo, Yiqun Zhou, Tianyi Liu, Wei Fu
Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.
糖尿病伤口愈合受损是再生医学面临的一个重大挑战,其特点是炎症持续时间长,组织修复能力不足,这主要是由偏向促炎的巨噬细胞表型造成的。本研究探讨了白细胞介素-10(IL-10)化学修饰mRNA(modRNA)富集的人脂肪衍生多能基质细胞(hADSCs)在糖尿病伤口小鼠模型中的治疗潜力。这项研究中使用的modRNA是用N1-甲基假尿嘧啶-5′-三磷酸(m1Ψ)代替尿苷-5-三磷酸进行化学修饰的。体外实验表明,转染了IL-10 modRNA的hADSCs能有效地调节巨噬细胞向抗炎表型极化。用一种成熟的小鼠模型进行的体内实验表明,在术后第5天(POD5)移植hADSCsmodIL-10能显著改善伤口愈合效果,包括加速伤口闭合、增强再上皮化、促进M2极化、改善胶原沉积和增加新生血管。这项研究的结论是,富含IL-10 modRNA的hADSCs为糖尿病伤口愈合提供了一种很有前景的治疗方法,而IL-10的给药时机对其有效性起着至关重要的作用。这些细胞能调节巨噬细胞的极化并促进组织修复,显示了它们改善糖尿病伤口管理的潜力。
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引用次数: 0
Bilayer 3D co‐culture platform inducing the differentiation of normal fibroblasts into cancer‐associated fibroblast like cells: New in vitro source to obtain cancer‐associated fibroblasts 诱导正常成纤维细胞分化为类似癌症相关成纤维细胞的双层三维共培养平台:获取癌症相关成纤维细胞的新体外来源
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-05 DOI: 10.1002/btm2.10708
Yeon Ju Kim, Hyeon Song Lee, Dohyun Kim, Hwa Kyung Byun, Woong Sub Koom, Won‐Gun Koh
This study presents a novel in vitro bilayer 3D co‐culture platform designed to obtain cancer‐associated fibroblasts (CAFs)‐like cells. The platform consists of a bilayer hydrogel structure with a collagen/polyethylene glycol (PEG) hydrogel for fibroblasts as the upper layer and an alginate hydrogel for tumor cells as the lower layer. The platform enabled paracrine interactions between fibroblasts and cancer cells, which allowed for selective retrieval of activated fibroblasts through collagenase treatment for further study. Fibroblasts remained viable throughout the culture periods and showed enhanced proliferation when co‐cultured with cancer cells. Morphological changes in the co‐cultured fibroblasts resembling CAFs were observed, especially in the 3D microenvironment. The mRNA expression levels of CAF‐related markers were significantly upregulated in 3D, but not in 2D co‐culture. Proteomic analysis identified upregulated proteins associated with CAFs, further confirming the transformation of normal fibroblasts into CAF within the proposed 3D co‐culture platform. Moreover, co‐culture with CAF induced radio‐ and chemoresistance in pancreatic cancer cells (PANC‐1). Survival rate of cancer cells post‐irradiation and gemcitabine resistance increased significantly in the co‐culture setting, highlighting the role of CAFs in promoting cancer cell survival and therapeutic resistance. These findings would contribute to understanding molecular and phenotypic changes associated with CAF activation and provide insights into potential therapeutic strategies targeting the tumor microenvironment.
本研究提出了一种新型体外双层三维共培养平台,旨在获得类似癌症相关成纤维细胞(CAFs)的细胞。该平台由双层水凝胶结构组成,上层是用于成纤维细胞的胶原/聚乙二醇(PEG)水凝胶,下层是用于肿瘤细胞的藻酸盐水凝胶。该平台实现了成纤维细胞和癌细胞之间的旁分泌相互作用,从而可以通过胶原酶处理选择性地回收活化的成纤维细胞,以便进行进一步研究。在整个培养过程中,成纤维细胞始终保持活力,与癌细胞共培养时,成纤维细胞的增殖能力增强。在共培养的成纤维细胞中观察到类似 CAF 的形态变化,尤其是在三维微环境中。CAF 相关标记物的 mRNA 表达水平在三维共培养中显著上调,而在二维共培养中则没有。蛋白质组分析发现了与 CAFs 相关的上调蛋白,进一步证实了在拟议的三维共培养平台中正常成纤维细胞向 CAF 的转化。此外,与 CAF 的共培养诱导了胰腺癌细胞(PANC-1)的放射和化疗抗性。在共培养环境中,癌细胞照射后的存活率和吉西他滨耐药性显著增加,这突出表明了CAFs在促进癌细胞存活和治疗耐药性方面的作用。这些发现有助于了解与CAF活化相关的分子和表型变化,并为针对肿瘤微环境的潜在治疗策略提供见解。
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引用次数: 0
Mesenchymal stem cells for osteoarthritis: Recent advances in related cell therapy 间充质干细胞治疗骨关节炎:相关细胞疗法的最新进展
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-05 DOI: 10.1002/btm2.10701
Jianjing Lin, Jingtao Huang, Zilu Jiao, Mengyuan Nian, Canfeng Li, Yali Dai, Shicheng Jia, Xintao Zhang
Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti‐inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration.
骨关节炎(OA)是一种影响整个关节的退行性关节疾病,一直是全球医疗系统的巨大负担。尽管传统疗法和靶向软骨细胞疗法在治疗 OA 和软骨再生方面取得了重大进展,但仍存在许多问题。来自各种组织的间充质干细胞是研究最多的细胞类型,已被用于OA的临床前和临床研究,因为与自体软骨细胞相比,间充质干细胞的来源更广泛、体外扩增能力更强、具有抗炎和免疫调节特性。本文将系统回顾这些领域的最新进展。它可能会为改善 OA 和软骨再生提供新的见解。
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引用次数: 0
Sperm quality analyzer: A portable LED array microscope with dark-field imaging 精子质量分析仪具有暗视野成像功能的便携式 LED 阵列显微镜
IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-02 DOI: 10.1002/btm2.10703
Meng Shao, Changxu Li, Xiaohao Ma, Haoyu Pan, Zeyu Ke, Rui Liu, Zhiguo Zhang, Min-Cheng Zhong, Yi Wang, Zhensheng Zhong, Fengya Lu, Xunbin Wei, Jinhua Zhou

Sperm quality analysis plays an important role in diagnosing infertility, which is widely implemented by computer-assisted sperm analysis (CASA) of sperm-swimming imaging from commercial phase-contrast microscopy. A well-equipped microscope comes with a high cost, increasing the burden of assessment, and it also occupies a large volume. For point-of-care testing (POCT) of sperm quality, these factors are confronted with the challenges of low-cost and portable instruments. In this study, an encoded light-emitting diode (LED) array illumination is employed to achieve a portable microscope with multicontrast imaging for sperm quality analysis. This microscopy has dimensions of 16.5 × 14.0 × 25.0 cm, and its dark-field (DF) imaging provides high-contrast sperm image data which is suitable for CASA. According to DF imaging, we developed a software of LabCASA, which can used to assess the motility characteristics of sperm. Compared with TrackMate, the difference in motility parameters from our software was less than 10% in the coefficient of variation (CV). The sperm motility parameters vary with the chamber temperature, which further confirms the reliability of our system with DF imaging. The DF imaging provides strong robustness for tracking sperm's motion under different microscopes. For assessment of the motility parameters, our system can work at a lower cost with a plastic structure. This system with DF imaging is suitable for portable POCT of sperm quality analysis, which is highly cost-effective in resource-constrained circumstances.

精子质量分析在不孕症诊断中起着重要作用,目前广泛采用的是商用相差显微镜的精子游动成像计算机辅助精子分析(CASA)。设备齐全的显微镜价格昂贵,增加了评估负担,而且体积庞大。对于精子质量的护理点检测(POCT)来说,这些因素都面临着低成本和便携式仪器的挑战。在这项研究中,采用了编码发光二极管(LED)阵列照明技术,实现了用于精子质量分析的便携式多对比度成像显微镜。该显微镜的尺寸为 16.5 × 14.0 × 25.0 厘米,其暗视野(DF)成像可提供适合 CASA 的高对比度精子图像数据。根据暗视野成像技术,我们开发了 LabCASA 软件,用于评估精子的运动特性。与 TrackMate 相比,我们软件的精子活力参数变异系数(CV)相差不到 10%。精子运动参数随腔室温度的变化而变化,这进一步证实了我们的 DF 成像系统的可靠性。DF 成像技术为在不同显微镜下跟踪精子运动提供了强大的稳健性。在运动参数评估方面,我们的系统采用塑料结构,成本较低。这种带 DF 成像的系统适用于精子质量分析的便携式 POCT,在资源有限的情况下极具成本效益。
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引用次数: 0
Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer 深入了解癌症细胞外基质硬度的机制、调节和治疗意义
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-08-01 DOI: 10.1002/btm2.10698
Ximo Zhang, Abdullah Al‐Danakh, Xinqing Zhu, Dan Feng, Linlin Yang, Haotian Wu, Yingying Li, Shujing Wang, Qiwei Chen, Deyong Yang
The tumor microenvironment (TME) is critical for cancer initiation, growth, metastasis, and therapeutic resistance. The extracellular matrix (ECM) is a significant tumor component that serves various functions, including mechanical support, TME regulation, and signal molecule generation. The quantity and cross‐linking status of ECM components are crucial factors in tumor development, as they determine tissue stiffness and the interaction between stiff TME and cancer cells, resulting in aberrant mechanotransduction, proliferation, migration, invasion, angiogenesis, immune evasion, and treatment resistance. Therefore, broad knowledge of ECM dysregulation in the TME might aid in developing innovative cancer therapies. This review summarized the available information on major ECM components, their functions, factors that increase and decrease matrix stiffness, and related signaling pathways that interplay between cancer cells and the ECM in TME. Moreover, mechanotransduction alters during tumorogenesis, and current drug therapy based on ECM as targets, as well as future efforts in ECM and cancer, are also discussed.
肿瘤微环境(TME)对癌症的发生、生长、转移和治疗耐药性至关重要。细胞外基质(ECM)是一种重要的肿瘤成分,具有多种功能,包括机械支持、TME 调节和信号分子生成。ECM 成分的数量和交联状态是肿瘤发生发展的关键因素,因为它们决定了组织的僵硬程度以及僵硬的 TME 与癌细胞之间的相互作用,从而导致异常的机械传导、增殖、迁移、侵袭、血管生成、免疫逃避和耐药性。因此,广泛了解 TME 中 ECM 的失调可能有助于开发创新的癌症疗法。本综述总结了现有关于 ECM 主要成分、其功能、增加和降低基质硬度的因素以及癌细胞与 TME 中 ECM 之间相互作用的相关信号通路的信息。此外,还讨论了肿瘤发生过程中机械传导的变化、目前以 ECM 为靶点的药物疗法以及未来在 ECM 与癌症方面的努力。
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引用次数: 0
Development of a biocompatible 3D hydrogel scaffold using continuous liquid interface production for the delivery of cell therapies to treat recurrent glioblastoma 利用连续液体界面生产技术开发生物相容性三维水凝胶支架,用于递送细胞疗法治疗复发性胶质母细胞瘤
IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-07-30 DOI: 10.1002/btm2.10676
Lauren Kass, Morrent Thang, Yu Zhang, Cathleen DeVane, Julia Logan, Addis Tessema, Jillian Perry, Shawn Hingtgen

Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D-printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days in vitro. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins.

胶质母细胞瘤(GBM)是成人中最常见的原发性恶性脑肿瘤,预后极差,有效治疗方案有限。各种细胞疗法已成为治疗 GBM 的有希望的候选疗法,但由于肿瘤贩运能力差、移植效率低和全身毒性大等原因,这些疗法在临床上均告失败。在本研究中,我们设计、表征并测试了一种三维打印细胞递送平台,该平台可提高植入 GBM 切除腔的治疗细胞的存活率。我们利用连续液态界面生产(CLIP)技术生成了一种生物相容性三维水凝胶,并证明我们能有效地将神经干细胞(NSCs)播种到水凝胶表面,而且细胞在体外培养 14 天后能高密度增殖。我们的研究表明,在 CLIP 支架上播种的神经干细胞比自由注射的细胞在体内存活时间更长,植入 6 天后,其增殖密度比原来高出 20%。最后,我们证明,在小鼠 LN229 GBM 切除模型中,与单独使用支架或治疗细胞相比,CLIP 上播种的治疗成纤维细胞能更有效地抑制肿瘤生长并延长存活时间。这些充满希望的结果表明,利用 CLIP 设计具有各种特性的水凝胶,以控制不同类型细胞疗法的递送是很有潜力的。未来的工作将包括对材料的免疫反应进行更全面的评估,以及提高生物相容性水性树脂的打印分辨率。
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引用次数: 0
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