Qin Hu, Aneesha Acharya, Ho Cheung Shum, Wai Keung Leung, George Pelekos
{"title":"Gum-on-a-Chip Exploring Host-Microbe Interactions: Periodontal Disease Modeling and Drug Discovery.","authors":"Qin Hu, Aneesha Acharya, Ho Cheung Shum, Wai Keung Leung, George Pelekos","doi":"10.1177/20417314251314356","DOIUrl":"10.1177/20417314251314356","url":null,"abstract":"<p><p>Periodontal disease is a pervasive and serious health issue, affecting millions globally and leading to severe oral and systemic health complications. This underscores the urgent need to thoroughly understand the complex host-microbe interactions involved. Developing models that allow crosstalk among various bacteria, periodontal component cells, and circulating immune cells is crucial for investigating periodontal disease and discovering new treatments. This study aimed to develop a biomimetic gum tissue model. Within four days, a bio-fabricated tissue with well-established barrier and immune functions was created. In this model, the key periodontal pathogen, <i>Porphyromonas gingivalis</i>, was observed to suppress the recruitment and migration of immune cells and dysregulate CD14 expression in THP-1 cells, leading to significant inflammation and tissue damage. Conversely, the probiotic <i>Akkermansia muciniphila</i> enhanced the host's defensive immune response, highlighting its potential as a therapeutic agent in periodontal disease.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251314356"},"PeriodicalIF":6.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615802","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}
Benedikt Fuchs, Sinan Mert, Daniel Hofmann, Constanze Kuhlmann, Alexandra Birt, Paul Severin Wiggenhauser, Riccardo E Giunta, Myra N Chavez, Jörg Nickelsen, Thilo Ludwig Schenck, Nicholas Moellhoff
{"title":"Bioactivated scaffolds promote angiogenesis and lymphangiogenesis for dermal regeneration in vivo.","authors":"Benedikt Fuchs, Sinan Mert, Daniel Hofmann, Constanze Kuhlmann, Alexandra Birt, Paul Severin Wiggenhauser, Riccardo E Giunta, Myra N Chavez, Jörg Nickelsen, Thilo Ludwig Schenck, Nicholas Moellhoff","doi":"10.1177/20417314251317542","DOIUrl":"10.1177/20417314251317542","url":null,"abstract":"<p><p>Chronic wounds represent an unresolved medical challenge with significant impact for patients' quality of life and global healthcare. Diverse in origin, ischemic-hypoxic and inflammatory conditions play central roles as pathological features that impede proper tissue regeneration. In this study, we propose an innovative approach to address this challenge. Our novel strategy utilizes photosynthetic biomaterials to restore the wound healing process firstly by promoting a normoxic, regeneration-supporting environment and secondly by mitigating inflammation through restoring lymphatic fluid transport and improving blood perfusion. We designed bioartificial scaffolds with photosynthetic cyanobacteria (Syn<i>echococcus sp. PCC</i> 7002) and assessed their functional integration in a bilateral full-thickness skin defect on the backs of mice over a period of 7 days. Illuminated photosynthetic cyanobacteria facilitated local tissue oxygenation independent of blood perfusion. Additionally, genetic modification enabled the secretion of lymphangiogenic hyaluronic acid (HA) into the wound area. After 7 days, the scaffolds were explanted and histologically examined, assessing cell migration (HE staining) and protein expression (CD31, LYVE-1, VEGFR3, Ly6G, and F4/80). Results demonstrated successful colonization of bioartificial scaffolds with cyanobacteria. Following implantation into bilateral full-thickness skin defects, we observed an adherent vascularized basal layer beneath the bioactivated scaffolds after 7 days. Substantial increases in cell migration within bacteria-loaden scaffolds were noted, accompanied by a heightened expression of lymphatic (LYVE-1 and VEGFR3) and endothelial cell markers (CD31). Simultaneously, an augmented expression of acute (Ly6G) and late (F4/80) inflammatory proteins was observed. In summary, we developed a viable photosynthetic scaffold by integrating cyanobacteria into dermal regeneration materials (DRM), promoting the expression of lymphatic, endothelial, and inflammatory proteins under hypoxic conditions. The findings from this study represent a significant advancement in establishing autotrophic tissue engineering approaches, advocating for the use of photosynthetic cells in treating a broad spectrum of hypoxic conditions.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251317542"},"PeriodicalIF":6.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615728","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}
Camille Scherrer, Camille Loret, Nicolas Védrenne, Colman Buckley, Anne-Sophie Lia, Vincent Kermene, Franck Sturtz, Frédéric Favreau, Amandine Rovini, Pierre-Antoine Faye
{"title":"From in vivo models to in vitro bioengineered neuromuscular junctions for the study of Charcot-Marie-Tooth disease.","authors":"Camille Scherrer, Camille Loret, Nicolas Védrenne, Colman Buckley, Anne-Sophie Lia, Vincent Kermene, Franck Sturtz, Frédéric Favreau, Amandine Rovini, Pierre-Antoine Faye","doi":"10.1177/20417314241310508","DOIUrl":"10.1177/20417314241310508","url":null,"abstract":"<p><p>Peripheral neuropathies are disorders affecting the peripheral nervous system. Among them, Charcot-Marie-Tooth disease is an inherited sensorimotor neuropathy for which no effective treatment exists yet. Research on Charcot-Marie-Tooth disease has been hampered by difficulties in accessing relevant cells, such as sensory and motor neurons, Schwann cells, and myocytes, which interact at the neuromuscular junction, the specialized synapses formed between nerves and skeletal muscles. This review first outlines the various in vivo models and methods used to study neuromuscular junction deficiencies in Charcot-Marie-Tooth disease. We then explore novel in vitro techniques and models, including complex hiPSC-derived cultures, which offer promising isogenic and reproducible neuromuscular junction models. The adaptability of in vitro culture methods, including cell origin, cell-type combinations, and choice of culture format, adds complexity and excitement to this rapidly evolving field. This review aims to recapitulate available tools for studying Charcot-Marie-Tooth disease to understand its pathophysiological mechanisms and test potential therapies.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314241310508"},"PeriodicalIF":6.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615801","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}
Yanchen Ye, Lin Huang, Kangjie Wang, Yunhao Sun, Zhihao Zhou, Tang Deng, Yunyan Liu, Rui Wang, Ridong Wu, Chen Yao
{"title":"Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia.","authors":"Yanchen Ye, Lin Huang, Kangjie Wang, Yunhao Sun, Zhihao Zhou, Tang Deng, Yunyan Liu, Rui Wang, Ridong Wu, Chen Yao","doi":"10.1177/20417314251315959","DOIUrl":"10.1177/20417314251315959","url":null,"abstract":"<p><p>Endothelial injury is a key factor initiating in-stent restenosis (ISR) following peripheral artery stent implantation. Genetically modified endothelial progenitor cells (EPCs) can promote reendothelialization of injured arteries and inhibit neointimal hyperplasia. However, the role of engineered EPCs overexpressing lncRNA H19 in these processes remains unclear. We constructed EPCs overexpressing lncRNA H19 and investigated their effects and mechanisms in promoting reendothelialization and inhibiting neointimal hyperplasia both <i>in vitro</i> and <i>in vivo</i>. Compared to the normal control group, ISR patients exhibited a significant reduction in circulating EPCs. Engineered EPCs overexpressing lncRNA H19 promoted reendothelialization and inhibited neointimal hyperplasia in injured arteries. Exogenous overexpression of lncRNA H19 significantly upregulated the endothelial repair-related gene S1PR3 in EPCs, while the opposite was also observed. Additionally, engineered EPCs overexpressing S1PR3 promoted reendothelialization and inhibited neointimal hyperplasia in injured arteries. S1PR3 overexpression enhanced EPCs proliferation, migration, and tube formation <i>in vitro</i>; these effects were lost with S1PR3 inhibition. Binding sites for H3K27 acetylation were identified on the S1PR3 promoter. Mechanistically, we found that lncRNA H19 directly interacted with HDAC2, a known H3K27ac deacetylase, disrupting its binding to H3K27 acetylation. Our findings suggest that lncRNA H19 positively regulates S1PR3 expression by disrupting HDAC2 / H3K27ac binding, thereby promoting reendothelialization of injured arteries and inhibiting neointimal hyperplasia.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251315959"},"PeriodicalIF":6.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458394","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}
Robyn A Macartney, Abijit Das, Atina G Imaniyyah, Annabelle Tr Fricker, Andrew M Smith, Stefano Fedele, Ipsita Roy, Hae-Won Kim, Dongjoon Lee, Jonathan C Knowles
{"title":"In vitro and ex vivo models of the oral mucosa as platforms for the validation of novel drug delivery systems.","authors":"Robyn A Macartney, Abijit Das, Atina G Imaniyyah, Annabelle Tr Fricker, Andrew M Smith, Stefano Fedele, Ipsita Roy, Hae-Won Kim, Dongjoon Lee, Jonathan C Knowles","doi":"10.1177/20417314241313458","DOIUrl":"10.1177/20417314241313458","url":null,"abstract":"<p><p>The benefit of complex 3D models to facilitate the robust testing of new drugs and drug delivery systems during the developmental stages of pharmaceutical manufacturing has recently become distinguished within the field. Recognition of this need by the pharmaceutical industry has provided a motivation for research into the development of reliable complex models for use in drug delivery, biomaterials, and tissue engineering. Both 3D in vitro and ex vivo models can enhance drug-testing and discovery prospects over the more traditionally used 2D, monolayer culture systems and animal models. Despite the widespread acceptance that 3D tissue modelling is advantageous in this field, there remains a lack of standardisation in the models throughout literature. This article provides an extensive review of current literature on in vitro, and ex vivo models of the oral mucosa for drug delivery applications; the advantages, limitations, and recommendations for future development of improved models for this application.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314241313458"},"PeriodicalIF":6.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408970","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":"Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells.","authors":"Peng Wang, Haiyue Zhao, Wei Chen, Yuhui Guo, Shuo Zhang, Xin Xing, Shuai Yang, Fengkun Wang, Juan Wang, Zengwu Shao, Yingze Zhang","doi":"10.1177/20417314241312563","DOIUrl":"10.1177/20417314241312563","url":null,"abstract":"<p><p>Osteoarthritis (OA) is an age-related chronic inflammatory disease, predominantly characterized by chondrocyte senescence and extracellular matrix (ECM) degradation. Although mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) are promising for promoting cartilage regeneration, their clinical application is limited by inconsistent therapeutic effects and insufficient targeting capabilities. Mechanical loading shows potential to optimize MSC-EVs for OA treatment, while the underlying mechanism is not clear. In this study, EVs derived from mechanical loading-primed MSCs (ML-EVs) demonstrate prominent efficacy in maintaining ECM homeostasis and relieving chondrocyte senescence, thereby mitigating OA. Subsequent miRNA sequencing reveals that ML-EVs exert their effects by delivering miR-27b-3p, which targets ROR1 mRNA in chondrocytes and suppresses downstream NF-κB pathways. By modulating the ROR1/NF-κB axis, miR-27b-3p effectively restrains ECM degradation and chondrocyte senescence. To optimize therapeutic efficacy of EVs, miR-27b-3p is overexpressed within EVs (miR<sup>OE</sup>-EVs), and a chondrocyte-targeted peptide (CTP) is conjugated to their surface, thereby constructing dual-engineered chondrocyte-targeted EVs (CTP/miR<sup>OE</sup>-EVs). CTP/miR<sup>OE</sup>-EVs exhibit excellent ability to specifically target cartilage and ameliorate OA pathology. In conclusion, this study underscores the critical role of mechanical loading in augmenting effectiveness of EVs in mitigating OA and introduces dual-engineered EVs that specifically target chondrocytes, providing a promising therapeutic strategy for OA.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314241312563"},"PeriodicalIF":6.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382676","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":"Dissolving microneedle patch loaded with adipokines-enriched adipose extract relieves atopic dermatitis in mouse via modulating immune disorders, microbiota imbalance, and skin barrier defects.","authors":"Jingyan Guan, Kaiqi Chen, Feng Lu, Yunfan He","doi":"10.1177/20417314241312511","DOIUrl":"10.1177/20417314241312511","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic relapsing dermatosis that demands new therapies. This research group previously developed a physically extracted adipose-derived extracellular matrix named adipose collagen fragments (ACF), which was determined containing massive adipose matrix-bound adipokines and medicable on AD through intradermal injection. However, problems concerning the control of drug release and inevitable pain caused by injection hinder the application of ACF in clinics. Microneedle (MN) is a rapid developing technique for precise and painless transdermal drug delivery. Therefore, a dissolving methacrylated gelatin/hyaluronic acid MN patch loaded with ACF was developed in this study. The morphological characteristics, mechanical properties, penetration ability, as well as biocompatibility and degradation efficiency of ACF-MN were evaluated, and its efficacy on ovalbumin-induced AD mice was also investigated. ACF-MN exhibited excellent penetration ability, biocompatibility, degradation efficiency, and satisfying efficacy on murine AD similar with fresh-made ACF. Furthermore, RNA-Seq combining bioinformatics were performed for mechanism exploration. ACF treatment showed a comprehensive efficacy on AD via restoring inflammatory dysregulation, microbiota imbalance, and skin barrier defects. This study offered a novel MN-based ACF-bound adipokines transdermal delivery system that may serve as a promising strategy for relieving AD.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314241312511"},"PeriodicalIF":6.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365186","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}
Jayson Sueters, Rowan van Heiningen, Ralph de Vries, Zeliha Guler, Judith Huirne, Theo Smit
{"title":"Advances in tissue engineering of peripheral nerve and tissue innervation - a systematic review.","authors":"Jayson Sueters, Rowan van Heiningen, Ralph de Vries, Zeliha Guler, Judith Huirne, Theo Smit","doi":"10.1177/20417314251316918","DOIUrl":"10.1177/20417314251316918","url":null,"abstract":"<p><p>Although various options are available to treat injured organs and peripheral nerves, none is without limitations. Auto- and allografts are the first choice of treatment, but tissue survival or functionality is not guaranteed due to often limited vascular and neural networks. In response, tissue-engineered solutions have been developed, yet clinical translations is rare. In this study, a systematic review was performed on tissue-engineered advancements for peripheral nerves and tissues, to aid future developments in bridging the gap toward the clinic by identifying high-potential solutions and unexplored areas. A systematic search was performed in PubMed, Embase, Web of Science, and Scopus until November 9, 2023. Search terms involved \"tissue engineering,\" \"guided,\" \"tissue scaffold,\" and \"tissue graft,\" together with \"innervation\" and \"reinnervation.\" Original in vivo or in vitro studies meeting the inclusion criteria (tissue-engineered peripheral nerve/innervation of tissue) and no exclusion criteria (no full text available; written in foreign language; nonoriginal article; tissue-engineering of central nervous system; publication before 2012; insufficient study quality or reproducibility) were assessed. A total of 68 out of 3626 original studies were included. Data extraction was based on disease model, cell origin and host species, biomaterial nature and composition, and external stimuli of biological, chemical or physical origin. Although tissue engineering is still in its infancy, explored innervation strategies of today were highlighted with respect to biomaterials, cell types, and external stimuli. The findings emphasize that natural biomaterials, pre-seeding with autologous cell sources, and solutions for reproductive organs are beneficial for future research. Natural biomaterials possess important cues required for cell-material interaction and closely resemble native tissue in terms of biomechanical, geometrical and chemical composition. Autologous cells induce biomaterial functionalization. As these solutions pose no risk of immunorejection and have demonstrated good outcomes, they are most likely to fulfill the clinical demands.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251316918"},"PeriodicalIF":6.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255846","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":"Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures.","authors":"Rasika S Murkar, Cornelia Wiese-Rischke, Tobias Weigel, Sascha Kopp, Heike Walles","doi":"10.1177/20417314241299076","DOIUrl":"10.1177/20417314241299076","url":null,"abstract":"<p><p>Advanced in vitro models are crucial for studying human airway biology. Our objective was the development and optimization of 3D in vitro models representing diverse airway regions, including deep lung alveolar region. This initiative was aimed at assessing the influence of selective scaffold materials on distinct airway co-culture models. While PET membranes (30 µm thickness) were unsuitable for alveolar models due to their stiffness and relatively high Young's modulus, a combination of collagenous scaffolds seeded with Calu-3 cells and fibroblasts, showed increased mucus production going from week 1 to week 4 of air lift culture. Meanwhile standard electrospun polymer membrane (50-60 µm thick), which possesses a considerably low modulus of elasticity, offered higher flexibility and supported co-cultures of primary alveolar epithelial (huAEC) and endothelial cells (hEC) in concert with lung biopsy-derived fibroblasts which enhanced maturation of the tissue model. As published, designing human alveolar in vitro models require thin scaffold to mimic the required ultra-thin ECM, in addition to assuring right balanced AT1/AT2 ratio for biomimetic representation. We concluded that co-cultivation of primary/stem cells or cell lines has a higher influence on the function of the airway tissue models than the applied scaffolds.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314241299076"},"PeriodicalIF":6.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066089","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}
Youliang Shen, Yuelei Wang, Yidan Xu, Jie Wang, Chuqiang Yin, Zengshuai Han, Feng Shen, Ting Wang
{"title":"Therapeutic potential and mechanisms of umbilical cord mesenchymal stem cells differentiating into tendon cells and promotion of rotator cuff tendon-bone healing.","authors":"Youliang Shen, Yuelei Wang, Yidan Xu, Jie Wang, Chuqiang Yin, Zengshuai Han, Feng Shen, Ting Wang","doi":"10.1177/20417314251315185","DOIUrl":"https://doi.org/10.1177/20417314251315185","url":null,"abstract":"<p><p>Rotator cuff tendon injuries often lead to shoulder pain and dysfunction. Traditional treatments such as surgery and physical therapy can provide temporary relief, but it is difficult to achieve complete healing of the tendon, mainly because of the limited repair capacity of the tendon cells. Therefore, it is particularly urgent to explore new treatment methods. In vitro experiments were performed to explore the mechanism of differentiation of umbilical cord mesenchymal stem cells (UCMSCs) to tendon cells and to evaluate their potential in promoting rotator cuff injury repair. Growth factors such as CTGF, GDF-6, and GDF-7 were used to induce the differentiation of UCMSCs, and gene expression changes during the differentiation process were analyzed by single-cell sequencing. Hes1 overexpression and animal models were constructed to study its role in UCMSCs differentiation and rotator cuff injury repair. CTGF was the optimal factor for inducing the differentiation of UCMSCs into tendon cells. With increasing induction time, UCMSCs exhibited obvious tendon cell characteristics, such as changes in cell morphology and increased expression of tendon-specific proteins (MKX, SCX, and TNC). Single-cell sequencing analysis revealed key cellular subpopulations and signaling pathways during differentiation. Furthermore, overexpression of the Hes1 gene significantly promoted the differentiation of UCMSCs to tendon cells and showed its therapeutic effect in rotator cuff injury repair in an animal model. This study confirmed the potential of UCMSCs in tendon injury repair, especially the critical role of Hes1 in promoting UCMSCs differentiation and rotator cuff tendon-bone healing, which provides a theoretical basis and experimental rationale for the development of new cellular therapeutic strategies.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251315185"},"PeriodicalIF":6.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066180","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}