Tissue Engineering Part A最新文献

{"title":"Induction of Fenestrae in Human Induced Pluripotent Stem Cell-Derived Endothelial Cells for Disease Modeling.","authors":"Elana M Meijer, Christian G M van Dijk, Rachel Giles, Karlijn Gijsen, Ihsan Chrifi, Marianne C Verhaar, Caroline Cheng","doi":"10.1089/ten.TEA.2023.0236","DOIUrl":"10.1089/ten.TEA.2023.0236","url":null,"abstract":"<p><p>The endothelial linings of capillaries, such as those in the kidney and small intestines, possess fenestrae that facilitate fluid and exchange of small molecules. Alterations in the size and number of endothelial fenestrae have been implicated in the pathogenesis of various diseases. The re-creation of fenestrated endothelium using human induced pluripotent stem cells (hiPSCs) provides a promising avenue to investigate the involvement of fenestrae in disease mechanisms and pharmacodynamics. In this project, we aim to induce the formation of fenestrae in nonfenestrated hiPSCs-derived endothelial cells (hiPSC-ECs). Vascular endothelial growth factor A (VEGFA) and phorbol myristate acetate (PMA) were used as inducers of fenestrae in hiPSC-ECs. The assessment of fenestrae formation included gene-expression analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunofluorescent staining. Endothelial monolayer functionality was evaluated by dextran permeability assays. Stimulation with VEGFA and PMA significantly induced expression of the diaphragmed fenestrae-associated marker, plasmalemmal vesicle-associated protein (PLVAP), in hiPSC-ECs at the mRNA, and protein levels. SEM analysis revealed VEGFA- and PMA-induced fenestrae structures on the cell membrane of hiPSC-ECs. The increased membrane localization of PLVAP visualized by TEM and immunofluorescent staining supported these findings. The induced fenestrated endothelium in hiPSC-ECs demonstrated selective passage of small solutes across a confluent monolayer with intact cell junctions, confirming functional competence. In conclusion, we present a novel methodology for inducing and regulating fenestrated endothelium in hiPSC-ECs. This innovative approach paves the way for the development of fenestrated microvasculature in human organ-on-a-chip systems, enabling complex disease modeling and physiologically relevant investigations of pharmacodynamics.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138833217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thirtieth Anniversary of Tissue Engineering: A Congratulations and a Few Thoughts.","authors":"Joseph P Vacanti","doi":"10.1089/ten.tea.2024.29054.jos","DOIUrl":"10.1089/ten.tea.2024.29054.jos","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Mechanisms of Vestibular Neuron Formation from Human Induced Pluripotent Stem Cells.","authors":"Benjamin Norton, Analia Quirk, Akihiro J Matsuoka","doi":"10.1089/ten.TEA.2023.0166","DOIUrl":"10.1089/ten.TEA.2023.0166","url":null,"abstract":"<p><p>The development of <i>in vitro</i> models that accurately recapitulate the complex cellular and molecular interactions of the inner ear is crucial for understanding inner ear development, function, and disease. In this study, we utilized a customized microfluidic platform to generate human induced pluripotent stem cell (hiPSC)-derived three-dimensional otic sensory neurons (OSNs). hiPSC-derived otic neuronal progenitors (ONPs) were cultured in hydrogel-embedded microfluidic channels over a 40-day period. Careful modulation of Wnt and Shh signaling pathways was used to influence dorsoventral patterning and direct differentiation toward a vestibular neuron lineage. After validating the microfluidic platform, OSN spheroid transcription factor and protein expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), immunocytochemistry, and flow cytometry. The results demonstrated the successful differentiation of hiPSCs into ONPs and subsequent divergent differentiation into vestibular neuronal lineages, as evidenced by the expression of characteristic markers. Overall, our microfluidic platform provides a physiologically relevant environment for the culture and differentiation of hiPSCs, offering a valuable tool for studying inner ear development, disease and drug screening, and regenerative medicine applications.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/β-Catenin.","authors":"Kehan Li, Linan Liu, Hanghang Liu, Jiawei Xing, Pei Hu, Jian Song","doi":"10.1089/ten.TEA.2023.0091","DOIUrl":"10.1089/ten.TEA.2023.0091","url":null,"abstract":"<p><p>The Hippo signaling pathway inhibits cell growth, and its components and functions are highly conserved in mammals. LATS1 is a core component of the Hippo signaling pathway associated with lymphatic invasion, astrogliosis, apoptosis, and autophagy. Nevertheless, the role of Hippo/LATS1 in osteogenesis remains unclear. In this study, we used ribonucleic acid (RNA) lentiviruses to inhibit the expression of <i>Lats1</i> in bone marrow-derived stem cells (BMSCs) and distraction osteogenic regions in rats. Increased osteogenic, proliferative, and migratory abilities of BMSCs were observed in <i>Lats1</i>-inhibited BMSCs, while these phenotypes were partially reversed by YAP1 inhibition. <i>In vivo</i>, we found that the LATS1/YAP1 axis promoted osteogenesis during distraction osteogenesis (DO). β-catenin was positively correlated with YAP1 expression <i>in vivo</i> and <i>in vitro</i>. When YAP1 was strongly positive in the nucleus, β-catenin expression was upregulated; when YAP1 expression was inhibited by verteporfin, β-catenin was not expressed in the nucleus. These findings suggest that the LATS1/YAP1 signaling axis promotes DO by activating the Wnt/β-catenin signaling pathway. This study provides insights into the molecular mechanism of osteogenesis and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-β-catenin.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaffold-Free Bone Marrow-Derived Mesenchymal Stem Cell Sheets Enhance Bone Formation in a Weight-Bearing Rat Critical Bone Defect Model.","authors":"Kazuaki Mito, Jordan Lachnish, Wei Le, Calvin Chan, Yun-Liang Chang, Jeffrey Yao","doi":"10.1089/ten.TEA.2023.0118","DOIUrl":"10.1089/ten.TEA.2023.0118","url":null,"abstract":"<p><p>Researchers have been exploring alternative methods for bone tissue engineering, as current management of critical bone defects may be a significant challenge for both patient and surgeon with conventional surgical treatments associated with several potential complications and drawbacks. Recent studies have shown mesenchymal stem cell sheets may enhance bone regeneration in different animal models. We investigated the efficacy of implanted scaffold-free bone marrow-derived mesenchymal stem cell (BMSC) sheets on bone regeneration of a critical bone defect in a weight-bearing rat model. BMSCs were isolated from the femora of male Sprague-Dawley rats 5-6 weeks of age and cell sheets were produced on temperature-responsive culture dishes. Nine male Sprague-Dawley rats 6-8 weeks of age were utilized. A bilateral femoral critical bone defect was created with a bridge plate serving as internal fixation. One side was randomly selected and BMSC sheets were implanted into the bone defect (BMSC group), with the contralateral side receiving no treatment (control). Rats were anesthetized and radiographs were performed at 2-week intervals. At the 8-week time point, rats were euthanized, femurs harvested, and microcomputed tomography and histological analysis was performed. We found a statistically significant increase in new bone formation and bone volume fraction compared with the control. Histomorphometry analysis revealed a larger percent of newly formed bone and a higher total histological score. Our results suggest that scaffold-free BMSC sheets may be used in the management of large weight-bearing bone defects to complement a different surgical technique or as a standalone approach followed by internal fixation. However, further research is still needed.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138453222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E2-Loaded Microcapsules and Bone Marrow-Derived Mesenchymal Stem Cells with Injectable Scaffolds for Endometrial Regeneration Application.","authors":"Yuelin Wu, Shengyi Gu, Jonathan M Cobb, Griffin H Dunn, Taylor A Muth, Chloe J Simchick, Baoguo Li, Wujie Zhang, Xiaolin Hua","doi":"10.1089/ten.TEA.2023.0238","DOIUrl":"10.1089/ten.TEA.2023.0238","url":null,"abstract":"<p><p>Bone marrow-derived mesenchymal stem cells (BMSCs) have been recognized as new candidates for the treatment of serious endometrial injuries. However, owing to the local microenvironment of damaged endometrium, transplantation of BMSCs yielded disappointing results. In this study, Pectin-Pluronic^® F-127 hydrogel as scaffolds were fabricated to provide three-dimensional architecture for the attachment, growth, and migration of BMSCs. E2 was encapsulated into the W/O/W microspheres to construct pectin-based E2-loaded microcapsules (E2 MPs), which has the potential to serve as a long-term reliable source of E2 for endometrial regeneration. Then, the BMSCs/E2 MPs/scaffolds system was injected into the uterine cavity of mouse endometrial injury model for treatment. At 4 weeks after transplantation, the system increased proliferative abilities of uterine endometrial cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive an embryo, suggesting that the BMSCs/E2 MPs/scaffolds system is a promising treatment option for endometrial regeneration. Furthermore, the mechanism of E2 in promoting the repair of endometrial injury was also investigated. Exosomes are critical paracrine mediators that act as biochemical cues to direct stem cell differentiation. In this study, it was found that the expression of endometrial epithelial cell (EEC) markers was upregulated in BMSCs treated by exosomes secreted from endometrial stromal cells (ESCs-Exos). Exosomes derived from E2-stimulated ESCs further promoted the expression level of EECs markers in BMSCs, suggesting exosomes released from ESCs by E2 stimulation could enhance the differentiation efficiency of BMSCs. Therefore, exosomes derived from ESCs play paracrine roles in endometrial regeneration stimulated by E2 and provide optimal estrogenic response.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Study of Immunodeficient Rat Strains in Engraftment of Human-Induced Pluripotent Stem Cell-Derived Airway Epithelia.","authors":"Yasuyuki Hayashi, Hiroe Ohnishi, Masayuki Kitano, Yo Kishimoto, Toshiaki Takezawa, Hideaki Okuyama, Masayoshi Yoshimatsu, Fumihiko Kuwata, Takeshi Tada, Keisuke Mizuno, Koichi Omori","doi":"10.1089/ten.TEA.2023.0214","DOIUrl":"10.1089/ten.TEA.2023.0214","url":null,"abstract":"<p><p>The airway epithelia (AE) play a role in the clearance of foreign substances through ciliary motility and mucus secreted. We developed an artificial trachea that is made of collagen sponges and polypropylene mesh for the regeneration of the tracheal defect, and it was used for a clinical study. Then, a model in which the luminal surface of an artificial trachea was covered with a human-induced pluripotent stem cell-derived AE (hiPSC-AE) was transplanted into the tracheal defect of nude rats to promote epithelialization. In the future, this model was expected to be applied to research on infectious diseases and drug discovery as a trachea-humanized rat model. However, at present, sufficient engraftment has not been achieved to evaluate functional recovery in transplanted cells. Therefore, this study focused on immunosuppression in recipient rats. Nude rats lack T cell function and are widely used for transplantation experiments; however, more severe immunosuppressed recipients are preferred for xenotransplantation. Several strains of immunodeficient rats were created as rats that exhibit more severe immunodeficiency until now. In this study, to establish a trachea-humanized rat model in which human AE function can be analyzed to improve engraftment efficiency, engraftment efficiency in nude rats and X-linked severe combined immunodeficiency (X-SCID) rats following hiPSC-AE transplantation was compared. In the analysis of the proportion of engrafted cells in total cells at the graft site, the engraftment efficiency of epithelial cells tended to be high in X-SCID rats, although no statistical difference was found between the two groups, whereas the engraftment efficiency of mesenchymal cells was higher in X-SCID rats. Furthermore, the number of immune cells that accumulated in the grafts showed that a pan T cell marker, that is, CD3-positive cells, did not differ between the two strains; however, CD45-positive cells and major histocompatibility complex (MHC) class II-positive cells significantly decreased in X-SCID rats. These results indicate that X-SCID rats are more useful for the transplantation of hiPSC-AE into the tracheae to generate trachea-humanized rat models.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production of a Bioink Containing Decellularized Spinal Cord Tissue for 3D Bioprinting.","authors":"Marcelo Garrido Dos Santos, Fernanda Stapenhorst França, João Pedro Prestes, Cristian Teixeira, Luiz Carlos Sommer, Laura Elena Sperling, Patricia Pranke","doi":"10.1089/ten.TEA.2023.0078","DOIUrl":"10.1089/ten.TEA.2023.0078","url":null,"abstract":"<p><p>For the past few years, three-dimensional (3D) bioprinting has emerged as a promising approach in the field of regenerative medicine. This technique allows for the production of 3D scaffolds to support cell transplantation due to its ability to mimic the extracellular environment. One alternative to enhancing cell adhesion, survival, and proliferation is the use of decellularized extracellular matrix as a bioink component. The aim of this study was to produce a bioink using lyophilized rat decellularized spinal cord tissue (DSCT) for 3D bioprinting of nervous tissue. DNA quantification, hematoxylin and eosin and DAPI staining indicated that 1% sodium dodecyl sulfate and 9 h processing were effective in removing the cells from the spinal cord samples. The cell viability assay showed that the decellularized matrix is not cytotoxic for PC12 cells. The hydrogel containing DSCT, alginate, and gelatine used as the base for the bioink has a shear thinning behavior and low G″/G' ratio, allowing for good printability without compromising cell viability after 3D bioprinting. The bioink supported long-term PC12 cell survival, with 93% of live cells 4 weeks after printing, and stimulated the production of laminin-1 and neurofilament-M. This bioink, therefore, represents an easily available biomaterial for central nervous system tissue engineering.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Call for Special Issue Papers:</i> Special Issue on Prof. Kyriacos Athanasiou in Celebration of Lifetime Achievement Award from TERMIS-AM.","authors":"Michael Detamore, Farshid Guilak, Gabriela Espinosa, Jerry Hu","doi":"10.1089/ten.tea.2023.29052.cfp","DOIUrl":"10.1089/ten.tea.2023.29052.cfp","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Mobilization and Local Stromal Cell-Derived Factor-1α Delivery Enhances Nascent Supraspinatus Muscle Fiber Growth.","authors":"Leah E Anderson, Liane E Tellier, Keshav R Shah, Joseph J Pearson, Alexandra L Brimeyer, Edward A Botchwey, Johnna S Temenoff","doi":"10.1089/ten.TEA.2023.0128","DOIUrl":"10.1089/ten.TEA.2023.0128","url":null,"abstract":"<p><p>Rotator cuff tear is a significant problem that leads to poor clinical outcomes due to muscle degeneration after injury. The objective of this study was to synergistically increase the number of proregenerative cells recruited to injure rotator cuff muscle through a novel dual treatment system, consisting of a bone marrow mobilizing agent (VPC01091), hypothesized to \"push\" prohealing cells into the blood, and localized delivery of stromal cell-derived factor-1α (SDF-1α), to \"pull\" the cells to the injury site. Immediately after rotator cuff tendon injury in rat, the mobilizing agent was delivered systemically, and SDF-1α-loaded heparin-based microparticles were injected into the supraspinatus muscle. Regenerative and degenerative changes to supraspinatus muscle and the presence of inflammatory/immune cells, mesenchymal stem cells (MSCs), and satellite cells were assessed via flow cytometry and histology for up to 21 days. After dual treatment, significantly more MSCs (31.9 ± 8.0% single cells) and T lymphocytes (6.7 ± 4.3 per 20 × field of view) were observed in supraspinatus muscle 7 days after injury and treatment compared to injury alone (14.4 ± 6.5% single cells, 1.2 ± 0.7 per 20 × field of view), in addition to an elevated M2:M1 macrophage ratio (3.0 ± 0.5), an indicator of a proregenerative environment. These proregenerative cellular changes were accompanied by increased nascent fiber formation (indicated by embryonic myosin heavy chain staining) at day 7 compared to SDF-1α treatment alone, suggesting that this method may be a promising strategy to influence the early cellular response in muscle and promote a proregenerative microenvironment to increase muscle healing after severe rotator cuff tear.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10818049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61566518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}