Tao Jiang, Shenghong Miao, Jingjie Shen, Wenjing Song, Shenglong Tan, Dandan Ma
{"title":"Enhanced effects of antagomiR-3074-3p-conjugated PEI-AuNPs on the odontogenic differentiation by targeting FKBP9.","authors":"Tao Jiang, Shenghong Miao, Jingjie Shen, Wenjing Song, Shenglong Tan, Dandan Ma","doi":"10.1177/20417314231184512","DOIUrl":"https://doi.org/10.1177/20417314231184512","url":null,"abstract":"<p><p>The odontogenic differentiation of dental pulp stem cells (DPSCs), which is vital for tooth regeneration, was regulated by various functional molecules. In recent years, a growing body of research has shown that miRNAs play a crucial role in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). However, the mechanisms by which miRNAs regulated odontogenic differentiation of hDPSCs remained unclear, and the application of miRNAs in reparative dentin formation in vivo was also rare. In this study, we first discovered that miR-3074-3p had an inhibitory effect on odontogenic differentiation of hDPSCs and antagomiR-3074-3p-conjugated PEI-AuNPs effectively promoted odontogenic differentiation of hDPSCs in vitro. AntagomiR-3074-3p-conjugated PEI-AuNPs was further applied to the rat pulp-capping model and showed the increased formation of restorative dentin. In addition, the results of lentivirus transfection in vitro suggested that FKBP9 acted as the key target of miR-3074-3p in regulating the odontogenic differentiation of hDPSCs. These findings might provide a new strategy and candidate target for dentin restoration and tooth regeneration.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231184512"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/7d/10.1177_20417314231184512.PMC10333998.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10304137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Desprez, Davide Danovi, Charles H Knowles, Richard M Day
{"title":"Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy.","authors":"Charlotte Desprez, Davide Danovi, Charles H Knowles, Richard M Day","doi":"10.1177/20417314221139794","DOIUrl":"https://doi.org/10.1177/20417314221139794","url":null,"abstract":"<p><p>Skeletal muscle-derived cells (SMDC) hold tremendous potential for replenishing dysfunctional muscle lost due to disease or trauma. Current therapeutic usage of SMDC relies on harvesting autologous cells from muscle biopsies that are subsequently expanded in vitro before re-implantation into the patient. Heterogeneity can arise from multiple factors including quality of the starting biopsy, age and comorbidity affecting the processed SMDC. Quality attributes intended for clinical use often focus on minimum levels of myogenic cell marker expression. Such approaches do not evaluate the likelihood of SMDC to differentiate and form myofibres when implanted in vivo, which ultimately determines the likelihood of muscle regeneration. Predicting the therapeutic potency of SMDC in vitro prior to implantation is key to developing successful therapeutics in regenerative medicine and reducing implementation costs. Here, we report on the development of a novel SMDC profiling tool to examine populations of cells in vitro derived from different donors. We developed an image-based pipeline to quantify morphological features and extracted cell shape descriptors. We investigated whether these could predict heterogeneity in the formation of myotubes and correlate with the myogenic fusion index. Several of the early cell shape characteristics were found to negatively correlate with the fusion index. These included total area occupied by cells, area shape, bounding box area, compactness, equivalent diameter, minimum ferret diameter, minor axis length and perimeter of SMDC at 24 h after initiating culture. The information extracted with our approach indicates live cell imaging can detect a range of cell phenotypes based on cell-shape alone and preserving cell integrity could be used to predict propensity to form myotubes in vitro and functional tissue in vivo.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314221139794"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9166700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenyun Song, Xinyu Chen, Jixin Ma, Hada Buhe, Yang Liu, Hexige Saiyin, Lixiang Ma
{"title":"Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids.","authors":"Chenyun Song, Xinyu Chen, Jixin Ma, Hada Buhe, Yang Liu, Hexige Saiyin, Lixiang Ma","doi":"10.1177/20417314221147113","DOIUrl":"https://doi.org/10.1177/20417314221147113","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is a fatal malignancy in the human abdominal cavity that prefers to invade the surrounding nerve/nerve plexus and even the spine, causing devastating and unbearable pain. The limitation of available in vitro models restricts revealing the molecular mechanism of pain and screening pain-relieving strategies to improve the quality of life of end-stage PC patients. Here, we report a PC nerve invasion model that merged human brain organoids (hBrO) with mouse PC organoids (mPCO). After merging hBrOs with mPCOs, we monitored the structural crosstalk, growth patterns, and mutual interaction dynamics of hBrO with mPCOs for 7 days. After 7 days, we also analyzed the pathophysiological statuses, including proliferation, apoptosis and inflammation. The results showed that mPCOs tend to approximate and intrude into the hBrOs, merge entirely into the hBrOs, and induce the retraction/shrinking of neuronal projections that protrude from the margin of the hBrOs. The approximating of mPCOs to hBrOs accelerated the proliferation of neuronal progenitor cells, intensified the apoptosis of neurons in the hBrOs, and increased the expression of inflammatory molecules in hBrOs, including NLRP3, IL-8, and IL-1β. Our system pathophysiologically replicated the nerve invasions in mouse GEMM (genetically engineered mouse model) primary and human PCs and might have the potential to be applied to reveal the molecular mechanism of nerve invasion and screen therapeutic strategies in PCs.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314221147113"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/ea/10.1177_20417314221147113.PMC9829995.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10525848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soraya Williams, Aveen R Jalal, Mark P Lewis, Owen G Davies
{"title":"A survey to evaluate parameters governing the selection and application of extracellular vesicle isolation methods.","authors":"Soraya Williams, Aveen R Jalal, Mark P Lewis, Owen G Davies","doi":"10.1177/20417314231155114","DOIUrl":"https://doi.org/10.1177/20417314231155114","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) continue to gain interest across the scientific community for diagnostic and therapeutic applications. As EV applications diversify, it is essential that researchers are aware of challenges, in particular the compatibility of EV isolation methods with downstream applications and their clinical translation. We report outcomes of the first cross-comparison study looking to determine parameters (EV source, starting volume, operator experience, application and implementation parameters such as cost and scalability) governing the selection of popular EV isolation methods across disciplines. Our findings highlighted an increased clinical focus, with 36% of respondents applying EVs in therapeutics and diagnostics. Data indicated preferential selection of ultracentrifugation for therapeutic applications, precipitation reagents in clinical settings and size exclusion chromatography for diagnostic applications utilising biofluids. Method selection was influenced by operator experience, with increased method diversity when EV research was not the respondents primary focus. Application and implementation criteria were indicated to be major influencers in method selection, with UC and SEC chosen for their abilities to process large and small volumes, respectively. Overall, we identified parameters influencing method selection across the breadth of EV science, providing a valuable overview of practical considerations for the effective translation of research outcomes.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231155114"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9104715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epidermis-on-a-chip system to develop skin barrier and melanin mimicking model.","authors":"Qiwei Li, Chunyan Wang, Xiaoran Li, Jing Zhang, Zilin Zhang, Keyu Yang, Jun Ouyang, Shaohui Zha, Lifeng Sha, Jianjun Ge, Zaozao Chen, Zhongze Gu","doi":"10.1177/20417314231168529","DOIUrl":"https://doi.org/10.1177/20417314231168529","url":null,"abstract":"<p><p>In vitro skin models are rapidly developing and have been widely used in various fields as an alternative to traditional animal experiments. However, most traditional static skin models are constructed on Transwell plates without a dynamic three-dimensional (3D) culture microenvironment. Compared with native human and animal skin, such in vitro skin models are not completely biomimetic, especially regarding their thickness and permeability. Therefore, there is an urgent need to develop an automated biomimetic human microphysiological system (MPS), which can be used to construct in vitro skin models and improve bionic performance. In this work, we describe the development of a triple-well microfluidic-based epidermis-on-a-chip (EoC) system, possessing epidermis barrier and melanin-mimicking functions, as well as being semi-solid specimen friendly. The special design of our EoC system allows pasty and semi-solid substances to be effectively utilized in testing, as well as allowing for long-term culturing and imaging. The epidermis in this EoC system is well-differentiated, including basal, spinous, granular, and cornified layers with appropriate epidermis marker (e.g. keratin-10, keratin-14, involucrin, loricrin, and filaggrin) expression levels in corresponding layers. We further demonstrate that this organotypic chip can prevent permeation of over 99.83% of cascade blue (a 607 Da fluorescent molecule), and prednisone acetate (PA) was applied to test percutaneous penetration in the EoC. Finally, we tested the whitening effect of a cosmetic on the proposed EoC, thus demonstrating its efficacy. In summary, we developed a biomimetic EoC system for epidermis recreation, which could potentially serve as a useful tool for skin irritation, permeability, cosmetic evaluation, and drug safety tests.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231168529"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/de/10.1177_20417314231168529.PMC10126702.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9369864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Shen, M Maggio, I Woods, M C Lowry, R Almasri, C Gorgun, K F Eichholz, E Stavenschi, K Hokamp, F M Roche, L O'Driscoll, D A Hoey
{"title":"Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism.","authors":"N Shen, M Maggio, I Woods, M C Lowry, R Almasri, C Gorgun, K F Eichholz, E Stavenschi, K Hokamp, F M Roche, L O'Driscoll, D A Hoey","doi":"10.1177/20417314231186918","DOIUrl":"https://doi.org/10.1177/20417314231186918","url":null,"abstract":"<p><p>Blood vessel formation is an important initial step for bone formation during development as well as during remodelling and repair in the adult skeleton. This results in a heavily vascularized tissue where endothelial cells and skeletal cells are constantly in crosstalk to facilitate homeostasis, a process that is mediated by numerous environmental signals, including mechanical loading. Breakdown in this communication can lead to disease and/or poor fracture repair. Therefore, this study aimed to determine the role of mature bone cells in regulating angiogenesis, how this is influenced by a dynamic mechanical environment, and understand the mechanism by which this could occur. Herein, we demonstrate that both osteoblasts and osteocytes coordinate endothelial cell proliferation, migration, and blood vessel formation via a mechanically dependent paracrine mechanism. Moreover, we identified that this process is mediated via the secretion of extracellular vesicles (EVs), as isolated EVs from mechanically stimulated bone cells elicited the same response as seen with the full secretome, while the EV-depleted secretome did not elicit any effect. Despite mechanically activated bone cell-derived EVs (MA-EVs) driving a similar response to VEGF treatment, MA-EVs contain minimal quantities of this angiogenic factor. Lastly, a miRNA screen identified mechanoresponsive miRNAs packaged within MA-EVs which are linked with angiogenesis. Taken together, this study has highlighted an important mechanism in osteogenic-angiogenic coupling in bone and has identified the mechanically activated bone cell-derived EVs as a therapeutic to promote angiogenesis and potentially bone repair.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231186918"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10467237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Panagiota Kakni, Barry Jutten, Daniel Teixeira Oliveira Carvalho, John Penders, Roman Truckenmüller, Pamela Habibovic, Stefan Giselbrecht
{"title":"Hypoxia-tolerant apical-out intestinal organoids to model host-microbiome interactions.","authors":"Panagiota Kakni, Barry Jutten, Daniel Teixeira Oliveira Carvalho, John Penders, Roman Truckenmüller, Pamela Habibovic, Stefan Giselbrecht","doi":"10.1177/20417314221149208","DOIUrl":"https://doi.org/10.1177/20417314221149208","url":null,"abstract":"<p><p>Microbiome is an integral part of the gut and is essential for its proper function. Imbalances of the microbiota can be devastating and have been linked with several gastrointestinal conditions. Current gastrointestinal models do not fully reflect the in vivo situation. Thus, it is important to establish more advanced in vitro models to study host-microbiome/pathogen interactions. Here, we developed for the first time an apical-out human small intestinal organoid model in hypoxia, where the apical surface is directly accessible and exposed to a hypoxic environment. These organoids mimic the intestinal cell composition, structure and functions and provide easy access to the apical surface. Co-cultures with the anaerobic strains <i>Lactobacillus casei</i> and <i>Bifidobacterium longum</i> showed successful colonization and probiotic benefits on the organoids. These novel hypoxia-tolerant apical-out small intestinal organoids will pave the way for unraveling unknown mechanisms related to host-microbiome interactions and serve as a tool to develop microbiome-related probiotics and therapeutics.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314221149208"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/d4/10.1177_20417314221149208.PMC9869231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10677635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Position Paper Progress in the development of biomimetic engineered human tissues.","authors":"Umber Cheema","doi":"10.1177/20417314221145663","DOIUrl":"https://doi.org/10.1177/20417314221145663","url":null,"abstract":"<p><p>Tissue engineering (TE) is the multi-disciplinary approach to building 3D human tissue equivalents in the laboratory. The advancement of medical sciences and allied scientific disciplines have aspired to engineer human tissues for three decades. To date there is limited use of TE tissues/organs as replacement body parts in humans. This position paper outlines advances in engineering of specific tissues and organs with tissue-specific challenges. This paper outlines the technologies most successful for engineering tissues and key areas of advancement.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314221145663"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9395400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Osteoarthritis models: From animals to tissue engineering.","authors":"Hongyuan Dou, Shuhan Wang, Jiawei Hu, Jian Song, Chao Zhang, Jiali Wang, Lin Xiao","doi":"10.1177/20417314231172584","DOIUrl":"https://doi.org/10.1177/20417314231172584","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic degenerative osteoarthropathy. Although it has been revealed that a variety of factors can cause or aggravate the symptoms of OA, the pathogenic mechanisms of OA remain unknown. Reliable OA models that accurately reflect human OA disease are crucial for studies on the pathogenic mechanism of OA and therapeutic drug evaluation. This review first demonstrated the importance of OA models by briefly introducing the OA pathological features and the current limitations in the pathogenesis and treatment of OA. Then, it mainly discusses the development of different OA models, including animal and engineered models, highlighting their advantages and disadvantages from the perspective of pathogenesis and pathology analysis. In particular, the state-of-the-art engineered models and their potential were emphasized, as they may represent the future direction in the development of OA models. Finally, the challenges in obtaining reliable OA models are also discussed, and possible future directions are outlined to shed some light on this area.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231172584"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/5d/10.1177_20417314231172584.PMC10201005.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10300124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modified black phosphorus quantum dots promotes spinal cord injury repair by targeting the AKT signaling pathway.","authors":"Dong-Mei Xie, Chuanwei Sun, Qingqiang Tu, Suyi Li, Yu Zhang, Xifan Mei, Yuanlong Li","doi":"10.1177/20417314231180033","DOIUrl":"https://doi.org/10.1177/20417314231180033","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious refractory disease of the central nervous system (CNS), which mostly caused by high-energy trauma. Existing interventions such as hormone shock and surgery are insufficient options, which relate to the secondary inflammation and neuronal dysfunction. Hydrogel with neuron-protective behaviors attracts tremendous attention, and black phosphorus quantum dots (BPQDs) encapsulating with Epigallocatechin-3-gallate (EGCG) hydrogels (E@BP) is designed for inflammatory modulation and SCI treatment in this study. E@BP displays good stability, biocompatibility and safety profiles. E@BP incubation alleviates lipopolysaccharide (LPS)-induced inflammation of primary neurons and enhances neuronal regeneration in vitro. Furthermore, E@BP reconstructs structural versus functional integrity of spinal cord tracts, which promotes recovery of motor neuron function in SCI rats after transplantation. Importantly, E@BP restarts the cell cycle and induces nerve regeneration. Moreover, E@BP diminishes local inflammation of SCI tissues, characterized by reducing accumulation of astrocyte, microglia, macrophages, and oligodendrocytes. Indeed, a common underlying mechanism of E@BP regulating neural regenerative and inflammatory responses is to promote the phosphorylation of key proteins related to AKT signaling pathway. Together, E@BP probably repairs SCI by reducing inflammation and promoting neuronal regeneration via the AKT signaling pathway.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231180033"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/62/10.1177_20417314231180033.PMC10272649.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}