Tissue Engineering Part A最新文献

筛选
英文 中文
Editorial for Special Issue on Artificial Intelligence in Tissue Engineering and Biology. 组织工程与生物学中的人工智能》特刊编辑。
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-29 DOI: 10.1089/ten.TEA.2024.0240
Jason L Guo, Michael Januszyk, Michael T Longaker
{"title":"Editorial for Special Issue on Artificial Intelligence in Tissue Engineering and Biology.","authors":"Jason L Guo, Michael Januszyk, Michael T Longaker","doi":"10.1089/ten.TEA.2024.0240","DOIUrl":"10.1089/ten.TEA.2024.0240","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006046","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}
引用次数: 0
The role of matrix stiffness and viscosity on lipid phenotype and fat lineage potential. 基质硬度和粘度对脂质表型和脂肪血统潜能的作用
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-21 DOI: 10.1089/ten.TEA.2024.0149
Chelsea Jane Stephens, Reina Kobayashi, Daniel C Berry, Jonathan T Butcher
{"title":"The role of matrix stiffness and viscosity on lipid phenotype and fat lineage potential.","authors":"Chelsea Jane Stephens, Reina Kobayashi, Daniel C Berry, Jonathan T Butcher","doi":"10.1089/ten.TEA.2024.0149","DOIUrl":"https://doi.org/10.1089/ten.TEA.2024.0149","url":null,"abstract":"<p><p>Autologous fat transfer is a common procedure that patients undergo to rejuvenate large soft tissue defects. However, these surgeries are complicated by limited tissue sources, donor-site morbidity, and necrosis. While the biofabrication of fat tissue can serve as a clinical option for reconstructive surgery, the influence of matrix mechanics, specifically stiffness and viscosity, on adipogenesis requires further elucidation. Additionally, the effects of these mechanical parameters on metabolic and thermogenic fat potential have yet to be investigated. Gelatin methacryloyl (GelMA) polymers with varying degrees of methacrylation (DoM) were fabricated to create matrices with different stiffnesses and viscosities. Human adipose-derived mesenchymal stem cells were then encapsulated in mechanically tunable GelMA and underwent adipogenesis to investigate the effects of matrix mechanics on lipid phenotype and fat potential. Mechanical testing confirmed that GelMA stiffness was regulated by DoM and weight composition, while viscosity was determined by the latter. Further work revealed that while lipid phenotype became more enriched as matrix stiffness and viscosity declined, the potential towards metabolic and thermogenic fat appeared to be more viscous-dependent rather than stiffness-dependent. Additionally, FABP4 and UCP1 gene expression exhibited viscous-dependent behavior despite comparable levels of PPARg. However, despite the superior role of viscosity, lipid quantity and mitochondrial abundance demonstrated stiffness-dependent behavior. Overall, this work revealed that matrix viscosity played a more superior role than stiffness in driving adipogenesis and distinguishing between metabolic and thermogenic fat potential. Ultimately, this differentiation in fat production is important for engineering ideal adipose tissue for large soft tissue defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010025","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}
引用次数: 0
Vascularization of Human Acellular Dermal Matrices: A Comparative Study in a Nonhuman Primate Model. 人类细胞真皮基质的血管化:非人灵长类动物模型比较研究
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-19 DOI: 10.1089/ten.TEA.2024.0059
Victoria Stefanelli, Jared Lombardi, Joselito Ferrer, Maryellen Gardocki-Sandor
{"title":"Vascularization of Human Acellular Dermal Matrices: A Comparative Study in a Nonhuman Primate Model.","authors":"Victoria Stefanelli, Jared Lombardi, Joselito Ferrer, Maryellen Gardocki-Sandor","doi":"10.1089/ten.TEA.2024.0059","DOIUrl":"10.1089/ten.TEA.2024.0059","url":null,"abstract":"<p><p>Four human acellular dermal matrices (hADMs) were characterized in a nonhuman primate abdominal wall repair model by evaluating host immune response, vascularization, and incorporation into host tissues. AlloDerm™ (electron beam-sterilized hADM [e-hADM]), AlloMax™ (gamma beam-sterilized hADM, freeze-dried [g-hADM-FD]), DermaMatrix™ (hADM, freeze-dried [hADM-FD]), and FlexHD™ (ethanol-treated hADM [EtOH-hADM]) were each implanted in an abdominal wall-bridging defect in nonhuman primates (<i>n</i> = 3 animals/time point, <i>n</i> = 36 animals). Immunohistochemical and histological assessments were conducted on biopsies from each hADM at 1-, 3-, and 6-months postimplantation to assess vascularization (hematoxylin and eosin [H&E], CD31, alpha smooth muscle actin [αSMA], collagen IV), inflammatory/immune response (H&E, CD3, CD20, CD68), and collagen turnover (H&E, matrix metalloproteinase-9 [MMP-9]). MMP-9 immunolabeling was similar among different hADMs at 1 month; however, hADM-FD and EtOH-hADM showed higher total mean MMP-9-immunopositive areas at approximately 16% compared with <1% for e-hADM and g-hADM at 6 months postimplantation. Cells that stained positively for CD68, CD3, and CD20 were generally higher for hADM-FD and EtOH-hADM compared with other hADMs. The mean CD31-immunopositive area, CD31 vessel density, CD31 vessel diameter, and collagen IV-immunopositive area increased over time. Among all the hADM types, e-hADM had the highest mean (±standard deviation [SD]) CD31-immunopositive area at 1.54% ± 1.01%, vessel density at 7.86 × 10<sup>-5</sup> ± 3.96 × 10<sup>-5</sup> vessels/µm<sup>2</sup>, and collagen IV-immunopositive area at 2.55% ± 0.73% 1-month postimplantation. The pattern of αSMA immunolabeling varied among the hADMs. Histology showed that overall inflammation was mild at 1 month. Overall fibroblast repopulation and collagen remodeling increased over time from 1 to 6 months postimplantation. Fibroblast infiltration was minimal to mild at 1 month, with e-hADM showing the highest mean (±SD) score at 2.00 ± 0.00 compared with other hADMs. Only hADM-FD was not completely replaced by neotissue formation at 6 months postimplantation. All hADMs promoted vascularization, cell infiltration, and incorporation into host tissue, which were associated with acute inflammation and immune responses, within a 6-month period. A trend toward relatively enhanced early vascularization in e-hADM compared with other hADMs was observed. Immunogenic responses among the hADMs in the present study showed a slight distinction toward more quiescent terminally sterilized hADMs (e-hADM, g-hADM-FD) versus aseptically processed hADMs (EtOH-hADM, hADM-FD).</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749810","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}
引用次数: 0
Mapping Biomaterial Complexity by Machine Learning. 通过机器学习绘制生物材料的复杂性。
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-12 DOI: 10.1089/ten.TEA.2024.0067
Eman Ahmed, Prajakatta Mulay, Cesar Ramirez, Gabriela Tirado-Mansilla, Eugene Cheong, Adam Gormley
{"title":"Mapping Biomaterial Complexity by Machine Learning.","authors":"Eman Ahmed, Prajakatta Mulay, Cesar Ramirez, Gabriela Tirado-Mansilla, Eugene Cheong, Adam Gormley","doi":"10.1089/ten.TEA.2024.0067","DOIUrl":"https://doi.org/10.1089/ten.TEA.2024.0067","url":null,"abstract":"<p><p>Biomaterials often have subtle properties that ultimately drive their bespoke performance. Given this nuanced structure-function behavior, the standard scientific approach of one experiment at a time or design of experiment (DOE) methods is largely inefficient for the discovery of complex biomaterials. More recently, high-throughput experimentation coupled with machine learning methods have matured beyond expert users allowing scientists and engineers from diverse backgrounds to access these powerful data science tools. As a result, we now have the opportunity to strategically utilize all available data from high- throughput experiments to train efficacious models and map the structure-function behavior of biomaterials for their discovery. Herein, we discuss this necessary shift to data-driven determination of structure-function properties of biomaterials as we highlight how machine learning is leveraged in identifying physicochemical cues for biomaterials in tissue engineering, gene delivery, drug delivery, protein stabilization, and antifouling materials. We also discuss data-mining approaches that are coupled with machine learning to map biomaterial functions that reduce the load on experimental approaches for faster biomaterial discovery. Ultimately, harnessing the prowess of machine learning will lead to accelerated discovery and development of optimal biomaterial designs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972340","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}
引用次数: 0
Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model. 在小鼠股骨骨折模型中通过局部冷疗法促进骨愈合
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-07 DOI: 10.1089/ten.TEA.2024.0069
Matthew Zakaria, Jerome Allard, Jose Garcia, Justin Matta, Yazan Honjol, Drew Schupbach, Michael Grant, Fackson Mwale, Edward Harvey, Geraldine Merle
{"title":"Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model.","authors":"Matthew Zakaria, Jerome Allard, Jose Garcia, Justin Matta, Yazan Honjol, Drew Schupbach, Michael Grant, Fackson Mwale, Edward Harvey, Geraldine Merle","doi":"10.1089/ten.TEA.2024.0069","DOIUrl":"10.1089/ten.TEA.2024.0069","url":null,"abstract":"<p><p>Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a 4-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared with controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase and transient receptor potential vanilloid 1. These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, noninvasive treatment strategy in orthopedic care.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749809","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}
引用次数: 0
Endothelial cells increase mesenchymal stem cell differentiation in scaffold-free 3D vascular tissue. 内皮细胞可促进无支架三维血管组织中间充质干细胞的分化。
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-07 DOI: 10.1089/ten.TEA.2024.0122
William Gabriel DeMaria, Andre Figueroa-Milla, Abigail Kaija, Anne E Harrington, Benjamin Tero, Larisa Ryzhova, Lucy Liaw, Marsha W Rolle
{"title":"Endothelial cells increase mesenchymal stem cell differentiation in scaffold-free 3D vascular tissue.","authors":"William Gabriel DeMaria, Andre Figueroa-Milla, Abigail Kaija, Anne E Harrington, Benjamin Tero, Larisa Ryzhova, Lucy Liaw, Marsha W Rolle","doi":"10.1089/ten.TEA.2024.0122","DOIUrl":"https://doi.org/10.1089/ten.TEA.2024.0122","url":null,"abstract":"<p><p>In this study, we present a versatile, scaffold-free approach to create ring-shaped engineered vascular tissue segments using human mesenchymal stem cell-derived smooth muscle cells (hMSC-SMCs) and endothelial cells (ECs). We hypothesized that incorporation of ECs would increase hMSC-SMC differentiation without compromising tissue ring strength or fusion to form tissue tubes. Undifferentiated hMSCs and ECs were co-seeded into custom ring-shaped agarose wells using four different concentrations of ECs: 0, 10, 20, and 30%. Co-seeded EC and hMSC rings were cultured in SMC differentiation medium for a total of 22 days. Tissue rings were then harvested for histology, western blotting, wire myography, and uniaxial tensile testing to examine their structural and functional properties. Differentiated hMSC tissue rings comprised of 20 and 30% ECs exhibited significantly greater SMC contractile protein expression, endothelin-1 (ET-1)-meditated contraction, and force at failure compared to the 0% EC rings. On average, the 0, 10, 20, and 30% EC rings exhibited a contractile force of 0.745 ± 0.117, 0.830 ± 0.358, 1.31 ± 0.353, and 1.67 ± 0.351 mN (mean ± SD) in response to ET-1, respectively. Additionally, the mean maximum force at failure for the 0, 10, 20, and 30% EC rings was 88.5 ± 36.2, 121 ± 59.1, 147 ± 43.1, and 206 ± 20.8 mN (mean ± SD), respectively. Based on these results, 30% EC rings were fused together to form tissue engineered blood vessels (TEBVs) and compared to 0% EC TEBV controls. The addition of 30% ECs in TEBVs did not affect ring fusion but did result in significantly greater SMC protein expression (calponin and smoothelin). In summary, co-seeding hMSCs with ECs to form tissue rings resulted in greater contraction, strength, and hMSC-SMC differentiation compared to hMSCs alone and indicates a method to create functional 3D human vascular cell co-culture model.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899052","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}
引用次数: 0
Bi-layered Adipose Mesenchymal Cell Sheets Improve Bladder Compliance in Spinal Cord-Injured Rats. 双层脂肪间充质细胞片改善脊髓损伤大鼠的膀胱顺应性
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-07 DOI: 10.1089/ten.TEA.2024.0115
Yuki Matsumoto, Tetsuya Imamura, Ryo Kitahara, Yoshihiro Inoue, Tetsuichi Saito, Manabu Ueno, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka
{"title":"Bi-layered Adipose Mesenchymal Cell Sheets Improve Bladder Compliance in Spinal Cord-Injured Rats.","authors":"Yuki Matsumoto, Tetsuya Imamura, Ryo Kitahara, Yoshihiro Inoue, Tetsuichi Saito, Manabu Ueno, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka","doi":"10.1089/ten.TEA.2024.0115","DOIUrl":"10.1089/ten.TEA.2024.0115","url":null,"abstract":"<p><p>To improve bladder compliance in patients with low-compliance bladders, augmentation cystoplasty with the intestinal tract is performed. However, the use of the intestinal tract often leads to serious surgical complications. Tissue engineering technologies have the potential to improve bladder compliance without using the intestinal tract. In this study, we fabricated bi-layered adipose-derived mesenchymal cell (AMC) sheets and then determined whether the bi-layered AMC sheets could improve bladder compliance in rats with spinal cord injury (SCI). The abdominal adipose tissues of green fluorescence protein (GFP)-transfected Sprague-Dawley (SD) rats were harvested, and the attached and proliferating cells on type I collagen were used as AMCs. The AMCs were then cultured on temperature-responsive culture dishes. After reaching over-confluence, the AMCs that maintained cell-cell contacts were detached from the dishes and applied to a gelatin hydrogel sheet. Then, another detached AMC monolayer was accumulated on the AMC monolayer-applied gelatin. Prior to 4 weeks of transplantation, the levels of T8-9 in the spinal cords of recipient SD rats were partially transected. After producing the bi-layered AMC sheets and the rats with SCI, the detrusor muscles of the anterior bladder walls of the rats with SCI were incised, and the bi-layered AMC sheet was patch-transplanted onto the exposed bladder epithelium (<i>n</i> = 8). As a control, the sham operation was performed (<i>n</i> = 7). Four weeks after the transplantation, bladder capacity and bladder compliance in AMC sheet-transplanted SCI rats were significantly higher than those in sham-operated control SCI rats. The smooth muscle layers in AMC sheet-transplanted bladders were significantly larger than those in control bladders. In addition, the collagen fibers in the AMC sheet-transplanted bladders were significantly smaller than those in the control bladders. Some GFP-positive transplanted AMCs differentiated into smooth muscle actin- or desmin-positive cells. Furthermore, GFP-positive cells secreted transforming growth factor-β1 or vascular endothelial growth factor. Therefore, this study showed that bi-layered AMC sheets could improve bladder compliance and bladder tissues in SCI rats.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749808","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}
引用次数: 0
Artificial Intelligence Applications in Oral Cancer and Oral Dysplasia. 人工智能在口腔癌和口腔发育不良中的应用。
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-07 DOI: 10.1089/ten.TEA.2024.0096
Chi T Viet, Michael Zhang, Neeraja Dharmaraj, Grace Y Li, Alexander T Pearson, Victoria A Manon, Anupama Grandhi, Ke Xu, Bradley E Aouizerat, Simon Young
{"title":"Artificial Intelligence Applications in Oral Cancer and Oral Dysplasia.","authors":"Chi T Viet, Michael Zhang, Neeraja Dharmaraj, Grace Y Li, Alexander T Pearson, Victoria A Manon, Anupama Grandhi, Ke Xu, Bradley E Aouizerat, Simon Young","doi":"10.1089/ten.TEA.2024.0096","DOIUrl":"10.1089/ten.TEA.2024.0096","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a highly unpredictable disease with devastating mortality rates that have not changed over the past decades, in the face of advancements in treatments and biomarkers, which have improved survival for other cancers. Delays in diagnosis are frequent, leading to more disfiguring treatments and poor outcomes for patients. The clinical challenge lies in identifying those patients at the highest risk of developing OSCC. Oral epithelial dysplasia (OED) is a precursor of OSCC with highly variable behavior across patients. There is no reliable clinical, pathological, histological, or molecular biomarker to determine individual risk in OED patients. Similarly, there are no robust biomarkers to predict treatment outcomes or mortality in OSCC patients. This review aims to highlight advancements in artificial intelligence (AI)-based methods to develop predictive biomarkers of OED transformation to OSCC or predictive biomarkers of OSCC mortality and treatment response. Biomarkers such as S100A7 demonstrate promising appraisal for the risk of malignant transformation of OED. Machine learning-enhanced multiplex immunohistochemistry workflows examine immune cell patterns and organization within the tumor immune microenvironment to generate outcome predictions in immunotherapy. Deep learning (DL) is an AI-based method using an extended neural network or related architecture with multiple \"hidden\" layers of simulated neurons to combine simple visual features into complex patterns. DL-based digital pathology is currently being developed to assess OED and OSCC outcomes. The integration of machine learning in epigenomics aims to examine the epigenetic modification of diseases and improve our ability to detect, classify, and predict outcomes associated with epigenetic marks. Collectively, these tools showcase promising advancements in discovery and technology, which may provide a potential solution to addressing the current limitations in predicting OED transformation and OSCC behavior, both of which are clinical challenges that must be addressed in order to improve OSCC survival.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749842","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}
引用次数: 0
Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4. 利用 TRPV4 的突变调节合成机制基因回路的反应
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-02 DOI: 10.1089/ten.TEA.2024.0163
Yu Seon Kim, Nancy Steward, Autumn Kim, Isabella Fehle, Farshid Guilak
{"title":"Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.","authors":"Yu Seon Kim, Nancy Steward, Autumn Kim, Isabella Fehle, Farshid Guilak","doi":"10.1089/ten.TEA.2024.0163","DOIUrl":"10.1089/ten.TEA.2024.0163","url":null,"abstract":"<p><p>Conventional gene therapy approaches for drug delivery generally rely on constitutive expression of the transgene and thus lack precise control over the timing and magnitude of delivery. Synthetic gene circuits with promoters that are responsive to user-defined stimuli can provide a molecular switch that can be utilized by cells to control drug production. Our laboratory has previously developed a mechanogenetic gene circuit that can deliver biological drugs, such as interleukin-1 receptor antagonist (IL-1Ra), on-demand through the activation of Transient receptor potential family, vanilloid 4 (TRPV4), a mechanosensory ion channel that has been shown to be activated transiently in response to physical stimuli such as physiological mechanical loading or hypo-osmotic stimuli. The goal of this study was to use mutations in TRPV4 to further tune the response of this mechanogenetic gene circuit. Human iPSC-derived chondrocytes harboring targeted gain-of-function mutations of TRPV4 were chondrogenically differentiated. Both mutants-V620I and T89I-showed greater total IL-1Ra production compared with wild type following TRPV4 agonist treatment, as well as mechanical or osmotic loading, but with altered temporal dynamics. Gene circuit output was dependent on the degree of TRPV4 activation secondary to GSK101 concentration or strain magnitude during loading. V620I constructs secreted more IL-1Ra compared with T89I across all experimental conditions, indicating that two mutations that cause similar functional changes to TRPV4 can result in distinct circuit activation profiles that differ from wild-type cells. In summary, we successfully demonstrate proof-of-concept that point mutations in TRPV4 that alter channel function can be used to tune the therapeutic output of mechanogenetic gene circuits.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617749","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}
引用次数: 0
Transcriptomics Demonstrates Significant Biological Effect of Growing Stem Cells on RGD-Cotton Scaffold. 转录组学证明干细胞在 RGD 棉花支架上生长具有显著的生物效应。
IF 3.5 3区 医学
Tissue Engineering Part A Pub Date : 2024-08-01 Epub Date: 2024-05-06 DOI: 10.1089/ten.TEA.2023.0333
Sihem Aouabdi, Taoufik Nedjadi, Rawiah Alsiary, Fouzi Mouffouk, Hifzur Rahman Ansari
{"title":"Transcriptomics Demonstrates Significant Biological Effect of Growing Stem Cells on RGD-Cotton Scaffold.","authors":"Sihem Aouabdi, Taoufik Nedjadi, Rawiah Alsiary, Fouzi Mouffouk, Hifzur Rahman Ansari","doi":"10.1089/ten.TEA.2023.0333","DOIUrl":"10.1089/ten.TEA.2023.0333","url":null,"abstract":"<p><p>Stem cell therapy provides a viable alternative treatment for degenerated or damaged tissue. Stem cells have been used either alone or in conjunction with an artificial scaffold. The latter provides a structural advantage by enabling the cells to thrive in three-dimensional (3D) settings, closely resembling the natural <i>in vivo</i> environments. Previously, we disclosed the development of a 3D scaffold made from cotton, which was conjugated with arginyl-glycyl-aspartic acid (RGD), to facilitate the growth and proliferation of mesenchymal stem cells (MSCs). This scaffold allowed the MSCs to adhere and proliferate without compromising their viability or their stem cell markers. A comprehensive analysis investigation of the molecular changes occurring in MSCs adhering to the cotton fibers will contribute to the advancement of therapy. The objective of this study is to analyze the molecular processes occurring in the growth of MSCs on a cotton-RGD conjugated-based scaffold by examining their gene expression profiles. To achieve this, we conducted an experiment where MSCs were seeded with and without the scaffold for a duration of 48 h. Subsequently, cells were collected for RNA extraction, cDNA synthesis, and whole-transcriptomic analysis performed on both populations. Our analysis revealed several upregulated and downregulated differently expressed genes in the MSCs adhering to the scaffold compared with the control cells. Through gene ontology analysis, we were able to identify enriched biological processes, molecular functions, pathways, and protein-protein interactions in these differentially expressed genes. Our data suggest that the scaffold may have the potential to enhance osteogenesis in the MSCs. Furthermore, our results indicate that the scaffold does not induce oxidative stress, inflammation, or aging in the MSCs. These findings provide valuable insights for the application of MSCs in tissue engineering and regenerative medicine.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872899","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信