Advanced Science
·
2023
·Vol. 10
·期 7
·2206101
·
IF 15.1
Jianguo Wu,Changming Chen,Chunlian Qin,Yihong Li,Nan Jiang,Qunchen Yuan,Yan Duan,Mengxue Liu,Xinwei Wei,Yiqun Yu,Liujing Zhuang,Ping Wang
Thanks to the gustatory system, humans can experience the flavors in foods and drinks while avoiding the intake of some harmful substances. Although great advances in the fields of biotechnology, microfluidics, and nanotechnologies have been made in recent years, this astonishing recognition system can hardly be replaced by any artificial sensors designed so far. Here, taste organoids are coupled with an extracellular potential sensor array to form a novel bioelectronic organoid and developed a taste organoids-on-a-chip system (TOS) for highly mimicking the biological sense of taste ex vivo with high stability and repeatability. The taste organoids maintain key taste receptors expression after the third passage and high cell viability during 7 days of on-chip culture. Most importantly, the TOS not only distinguishs sour, sweet, bitter, and salt stimuli with great specificity, but also recognizes varying concentrations of the stimuli through an analytical method based on the extraction of signal features and principal component analysis. It is hoped that this bioelectronic tongue can facilitate studies in food quality controls, disease modelling, and drug screening.
研究领域:
生物技术
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微流控技术
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纳米技术
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感觉生物学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Xinyuan Qin,Zhongqiao Gan,Haitao Liu,Tingting Tao,Jia He,Xianliang Li,Dong Shang,Xiang Li,Fuwei Xie,Jianhua Qin
Microgels are advanced scaffolds for tissue engineering due to their proper biodegradability, good biocompatibility, and high specific surface area for effective oxygen and nutrient transfer. However, most of the current monodispersed microgel fabrication systems rely heavily on various precision pumps, which highly increase the cost and complexity of their downstream application. In this work, we developed a simple and facile system for the controllable generation of uniform alginate microgels by integrating a gas-shearing strategy into a glass microfluidic device. Importantly, the cell-laden microgels can be rapidly prepared in a pump-free manner under an all-aqueous environment. The three-dimensional cultured green fluorescent protein-human A549 cells in alginate microgels exhibited enhanced stemness and drug resistance compared to those under two-dimensional conditions. The pancreatic cancer organoids in alginate microgels exhibited some of the key features of pancreatic cancer. The proposed microgels showed decent monodispersity, biocompatibility, and versatility, providing great opportunities in various biomedical applications such as microcarrier fabricating, organoid engineering, and high-throughput drug screening.
研究领域:
组织工程
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生物医学工程
·
细胞生物学
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癌症研究
·
药学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 41
·期 6
·953-963
·
IF 2.997
Xiunan Kong,Xiu Wang,Yumei Qin,Jianzhong Han
Sunset yellow (SY), an azo dye, is commonly used in the food industry. The scientific literature contains little information regarding the effects of SY on small intestinal epithelial cells (IECs). In this study, a small intestinal organoid model was used in in vitro toxicological studies of SY, and intestinal inflammatory responses in vivo to SY were investigated with the dextran sulfate sodium (DSS)-induced intestinal inflammation model in C57BL/6 mice. The intestinal organoids were cultured with 2 μg/ml SY for two generations, the growth rates were analyzed, and the expressions of cell lineages were assayed. For inflammatory responses, mice were fed with a diet containing 40 mg/kg diet SY and treated with 2.5% DSS for 7 days. The results showed that SY inhibited the growth of the organoids by inhibiting the proliferation and disturbing the differentiation of IECs. Furthermore, endoplasmic reticulum (ER) stress and oxidative stress levels were elevated in SY-treated organoids. In DSS-treated mice, the disease activity index and expression levels of interleukin-1β and tumor necrosis factor-α were enhanced in the SY group, concluding that SY exacerbated DSS-induced intestinal inflammation. Taken together, these findings revealed that SY could disturb the homeostasis of the small intestinal epithelium by generating high levels of ER stress and oxidative stress, with long-term continuous consumption of SY potentially increasing the risk of intestinal inflammation.
研究领域:
毒理学
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胃肠病学
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细胞生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Wenmin Chen,Yue Wu,Chuanyu Yang,Wenlong Ren,Lei Hou,Huichun Liang,Tingyue Wu,Yanjie Kong,Jiao Wu,Yu Rao,Ceshi Chen
Breast cancer is one of the most prevalent malignancies affecting women worldwide, underscoring the urgent need for more effective and specific treatments. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy to develop new lead compounds by selectively targeting oncoproteins for degradation. In this study, we designed, synthesized and evaluated a CRBN-based PROTAC, L055, which targets CDK9. Our findings demonstrate that L055 effectively inhibits the proliferation, induces cell cycle arrest, and decreases the survival of ERα-positive breast cancer cells in vitro. L055 specifically binds to CDK9, facilitating its degradation via the CRBN-dependent proteasomal pathway. Additionally, L055 suppressed the growth of organoids and tumors derived from T47D and MCF7 cells in nude mice. Thus, L055 represents a potential novel therapeutic agent for ERα-positive breast cancer and potentially other malignancies.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 7
·e18198
·
IF 4.3
Lingling Gao,Zheng Wei,Feiquan Ying,Lin Huang,Jingni Zhang,Si Sun,Zehua Wang,Jing Cai,Yuan Zhang
Mounting evidence has highlighted the multifunctional characteristics of glutamine metabolism (GM) in cancer initiation, progression and therapeutic regimens. However, the overall role of GM in the tumour microenvironment (TME), clinical stratification and therapeutic efficacy in patients with ovarian cancer (OC) has not been fully elucidated. Here, three distinct GM clusters were identified and exhibited different prognostic values, biological functions and immune infiltration in TME. Subsequently, glutamine metabolism prognostic index (GMPI) was constructed as a new scoring model to quantify the GM subtypes and was verified as an independent predictor of OC. Patients with low-GMPI exhibited favourable survival outcomes, lower enrichment of several oncogenic pathways, less immunosuppressive cell infiltration and better immunotherapy responses. Single-cell sequencing analysis revealed a unique evolutionary trajectory of OC cells from high-GMPI to low-GMPI, and OC cells with different GMPI might communicate with distinct cell populations through ligand-receptor interactions. Critically, the therapeutic efficacy of several drug candidates was validated based on patient-derived organoids (PDOs). The proposed GMPI could serve as a reliable signature for predicting patient prognosis and contribute to optimising therapeutic strategies for OC.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症治疗
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Wang Zhenxing,Liu Xuemin,Shi Xuetao,Wang Yingjun
To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models in vitro. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to in vitro thick tissue block models. This provides a robust foundation for future in vitro research and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.
研究领域:
组织工程
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再生医学
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生物医学研究
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生物打印
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Yujuan Zhu,Lingyu Sun,Xiao Fu,Junying Liu,Zhenjiang Liang,Hui Tan,Weiping Li,Yuanjin Zhao
Brain organoid is a promising technique with potential applications in developmental study, drug discovery and regenerative medicine, however, its practical values are restricted by poor flexibility, and lack of near-physiological structures or functions. Here, we present a multidisciplinary strategy to engineer novel vascularized human induced pluripotent stem cells (hiPSCs)-derived brain organoids system with biomimetic features using microfluidic hydrogel microcapsules. Due to the precise fluids control of microfluidic electrospray technology , its generated microcapsules enable the efficient encapsulation of hiPSCs-derived neural cells and formation of uniform human brain organoids. Through embedding microcapsules in hydrogel, vascularized brain organoids with structured organization and reasonable tissue size are established. We have found hiPSC-derived brain organoids with in vivo-like neural identity, brain region and layered cortex, as well as complex vascular networks, proving the capability to generate more relevant model of vascularized human brain. Thus, this biomimetic neural system could be injected for traumatic brain injury, and in vivo animal study has shown graft-to-host functional neural connectivity and neural regeneration, suggesting the organ-level functions for tissue repair. Our studies indicated that this simple, scalable and flexible system could be applied to develop biomimetic human tissues, which potentially advanced the organoid models for biomedical applications.
研究领域:
生物医学工程
·
神经科学
·
再生医学
·
干细胞研究
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DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Zhiyuan Wang,Renfeng Liu,Youjun Liu,Yuqi Zhao,Yuhao Wang,Botao Lu,Hui Li,Cheng Ju,Weidong Wu,Xinlin Gao,Hailiang Xu,Shixiang Cheng,Yulin Cao,Shuaijun Jia,Chunping Hu,Lei Zhu,Dingjun Hao
Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.
研究领域:
干细胞生物学
·
神经科学
·
组织工程
·
再生医学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haiyang Wang,Hao Zhuang,Chunyan Wu,Bangting Wang,Shijie Zhang,Yao Wang,Li Liu,Lianzhen Yu,Lei Zhang,Su Jing,Zhining Fan
The limited treatment options for colorectal cancer (CRC) and its adverse effects of chemotherapy underscore the urgent need for innovative therapeutic strategies. Focusing on early cellular glycosylation, particularly through the targeting of O-GlcNAcylation with small-molecule inhibitors, emerges as a promising direction. In this study, we developed artificial cell-like nanovesicles with a bilayer membrane structure to encapsulate OSMI-1, a specific inhibitor of O-GlcNAc transferase, aimed at inhibiting CRC progression. To enhance the effectiveness and specificity of the treatment, these self-targeted nanovesicles (T–Se–Lip–OSMI) were reinforced using internal diselenide bridges enabling redox-responsive release within the tumor microenvironment. In vitro assays revealed that T–Se–Lip–OSMI substantially diminished CRC cell proliferation, migration, and invasion. This was further validated using patient-derived organoid models, which highlighted the superior therapeutic efficacy of T–Se–Lip–OSMI over nanovesicles without the diselenide bridge. Subsequent in vivo studies confirmed its targeted delivery and pronounced suppression of tumor growth. Further mechanistic analysis illustrated that the therapeutic effect was mediated through the inhibition of O-GlcNAcylation of the Yes-associated protein (YAP), ultimately preventing the nuclear translocation of YAP and the activation of oncogenic downstream targets. This study leverages the unique properties of the diselenide bridge to enhance stability and functionality of the nanovesicles, offering a novel avenue for targeted CRC treatment.
研究领域:
癌症生物学
·
药学
·
分子生物学
·
纳米技术
·
细胞生物学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Chunlan Mu,Xiaoyong Li,Jiamei Yang,Geng G. Tian,Hepeng Bai,Wenhui Lin,Linhui Wang,Ji Wu
Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant-derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder-free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo-time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A-Eph receptor B2 ligand-receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant-derived compounds.
研究领域:
生殖生物学
·
分子生物学
·
基因组学
·
细胞生物学
·
不孕症研究
·
药理学
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DOI
PubMed
高影响因子
STAR Protocols
·
2022
·
IF 0
Mei-Mei Li,Fan-En Kong,Guang-Meng Li,Yi-Ti He,Xiao-Feng Zhang,Cheng-Yang Zhang,Jie-Kai Liang,Xin-Yuan Guan,Ning-Fang Ma,Mao-Bin Xie,Ming Liu
Summary Here, we present a detailed protocol for the identification of potential oncofetal targets for hepatocellular carcinoma (HCC) patients through a hepatocyte differentiation model and a sorafenib refractory cell-line-derived xenograft model. We describe the procedures of tumor sphere formation, organoid generation, and subcutaneous tumor formation for functional studies. We then detail the procedures of immunohistochemistry and immunofluorescence for examination of changes in lineage-specific markers. Finally, we describe the development of antibody-based therapeutics targeting tumor lineage plasticity in HCC. For complete details on the use and execution of this protocol, please refer to Kong et al. (2021). 1
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
细胞生物学
✓ 已验证
DOI
PubMed
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Weidong Wu,Youjun Liu,Renfeng Liu,Yuhao Wang,Yuqi Zhao,Hui Li,Botao Lu,Cheng Ju,Xinlin Gao,Hailiang Xu,Yulin Cao,Shixiang Cheng,Zhiyuan Wang,Shuaijun Jia,Chunping Hu,Lei Zhu,Dingjun Hao
The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.
研究领域:
神经科学
·
干细胞生物学
·
组织工程
·
再生医学
·
疾病建模
✓ 已验证
DOI
PubMed
高影响因子
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