Sang-Hyeon Nam, Ju Ang Kim, Soomin Lim, Su Jeong Lee, Chun-Ho Kim, Jong-Sup Bae, Yong Chool Boo, Young-Jin Kim, Eui Kyun Park
{"title":"Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model.","authors":"Sang-Hyeon Nam, Ju Ang Kim, Soomin Lim, Su Jeong Lee, Chun-Ho Kim, Jong-Sup Bae, Yong Chool Boo, Young-Jin Kim, Eui Kyun Park","doi":"10.1007/s13770-024-00657-x","DOIUrl":"10.1007/s13770-024-00657-x","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration.</p><p><strong>Methods: </strong>Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through alkaline phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis.</p><p><strong>Results: </strong>Glycine, glycine methyl ester, and glycinamide significantly enhanced collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to other combinations.</p><p><strong>Conclusion: </strong>GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1093-1107"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tae-Hee Kim, Min-Sung Kim, Nam-Gyun Kim, Nguyen Vu Linh, Hien Van Doan, Young-Mog Kim, Sang-Hyug Park, Won-Kyo Jung
{"title":"Multifunctional Microneedle Patch with Diphlorethohydroxycarmalol for Potential Wound Dressing.","authors":"Tae-Hee Kim, Min-Sung Kim, Nam-Gyun Kim, Nguyen Vu Linh, Hien Van Doan, Young-Mog Kim, Sang-Hyug Park, Won-Kyo Jung","doi":"10.1007/s13770-024-00655-z","DOIUrl":"10.1007/s13770-024-00655-z","url":null,"abstract":"<p><strong>Background: </strong>Treatment of skin wounds with diverse pathological characteristics presents significant challenges due to the limited specific and efficacy of current wound healing approaches. Microneedle (MN) patches incorporating bioactive and stimulus materials have emerged as a promising strategy to overcome these limitations and integrating bioactive materials with anti-bacterial and anti-inflammatory properties for advanced wound dressing.</p><p><strong>Methods: </strong>We isolated diphlorethohydroxycarmalol (DPHC) from Ishige okamurae and assessed its anti-inflammatory and anti-bacterial effects on macrophages and its antibacterial activity against Cutibacterium acnes. Subsequently, we fabricated polylactic acid (PLA) MN patches containing DPHC at various concentrations (0-0.3%) (PDPHC MN patches) and evaluated their mechanical properties and biological effects using in vitro and in vivo models.</p><p><strong>Resutls: </strong>Our findings demonstrated that DPHC effectively inhibited nitric oxide production in macrophages and exhibited rapid bactericidal activity against C. acnes. The PDPHC MN patches displayed potent antibacterial effects without cytotoxicity. Moreover, in 2,4-Dinitrochlorobenzene-stimulated mouse model, the PDPHC MN patches significantly suppressed inflammatory response and cutaneous lichenification.</p><p><strong>Conclusion: </strong>The results suggest that the PDPHC MN patches holds promise as a multifunctional wound dressing for skin tissue engineering, offering antibacterial properties and anti-inflammatory properties to promote wound healing process.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1007-1019"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reduced Cell Migration in Human Chondrocyte Sheets Increases Tissue Stiffness and Cartilage Protein Production.","authors":"Sopita Wongin-Sangphet, Pojchong Chotiyarnwong, Kwanchanok Viravaidya-Pasuwat","doi":"10.1007/s13770-024-00662-0","DOIUrl":"10.1007/s13770-024-00662-0","url":null,"abstract":"<p><strong>Background: </strong>Chondrogenic differentiation medium (CDM) is usually used to maintain chondrogenic activity during chondrocyte sheet production. However, tissue qualities remain to be determined as to what factors improve cell functions. Moreover, the relationship between CDM and cell migration proteins has not been reported.</p><p><strong>Method: </strong>In this study, the effect of CDM on the behavior of chondrocyte sheets was investigated. Structural analysis, mechanical testing and proteomics were performed to observe tissue qualities. The relationship between CDM and cell migration proteins were investigated using time-lapse observations and bioinformatic analysis.</p><p><strong>Results: </strong>During 48 h, CDM affected the chondrocyte behaviors by reducing cell migration. Compared to the basal medium, CDM impacted the contraction of monolayered chondrocyte sheets. At day 7, the contracted sheets increased tissue thickness and improved tissue stiffness. Cartilage specific proteins were also upregulated. Remarkedly, the chondrocyte sheets in CDM displayed downregulated proteins related to cell migration. Bioinformatic analysis revealed that TGFβ1 was shown to be associated with cartilage functions and cell migration. Pathway analysis of chondrocyte sheets in CDM also revealed the presence of a TGFβ pathway without activating actin production, which might be involved in synthesizing cartilage-specific proteins. Cell migration pathway showed MAPK signaling in both cultures of the chondrocyte sheets.</p><p><strong>Conclusion: </strong>Reduced cell migration in the chondrocyte sheet affected the tissue quality. Using CDM, TGFβ1 might trigger cartilage protein production through the TGFβ pathway and be involved in cell migration via the MAPK signaling pathway. Understanding cell behaviors and their protein expression would be beneficial for developing high-quality tissue-engineered cartilage.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1021-1036"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuai Peng, Xiangyang Liu, Lei Chang, Bin Liu, Mingyan Zhang, Yan Mao, Xiongjie Shen
{"title":"Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.","authors":"Shuai Peng, Xiangyang Liu, Lei Chang, Bin Liu, Mingyan Zhang, Yan Mao, Xiongjie Shen","doi":"10.1007/s13770-024-00663-z","DOIUrl":"10.1007/s13770-024-00663-z","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence supports the potential of exosomes as a promising therapeutic approach for intervertebral disc degeneration (IDD). Nevertheless, enhancing the efficiency of exosome treatment remains an urgent concern. This study investigated the impact of quercetin on the characteristics of mesenchymal stem cells (MSCs) and their released exosomes.</p><p><strong>Methods: </strong>Exosomes were obtained from quercetin pre-treated MSCs and quantified for the production based on nanoparticle tracking and western blot analysis. The molecules involved in the secretion and cargo sorting of exosomes were investigated using western blot and immunofluorescence analysis. Based on the in vitro biological analysis and in vivo histological analysis, the effects of exosomes derived from conventional or quercetin-treated MSCs on nucleus pulposus (NP) cells were compared.</p><p><strong>Results: </strong>A significant enhancement in the production and transportation efficiency of exosomes was observed in quercetin-treated MSCs. Moreover, the exosomes derived from quercetin-treated MSCs exhibited a greater abundance of antioxidant proteins, specifically superoxide dismutase 1 (SOD1), which inhibit the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in NP cells. Through in vitro and in vivo experiments, it was elucidated that exosomes derived from quercetin-treated MSCs possessed enhanced anti-inflammatory and antioxidant properties.</p><p><strong>Conclusion: </strong>Collectively, our research underscores an optimized therapeutic strategy for IDD utilizing MSC-derived exosomes, thereby augmenting the efficacy of exosomes in intervertebral disc regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1061-1077"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuyang Tang, Sen Yang, Zhen Qiu, Li Guan, Yigui Wang, Guixin Li, Yuanyu Tu, Lijuan Guo
{"title":"Rapamycin Attenuates H<sub>2</sub>O<sub>2</sub>-Induced Oxidative Stress-Related Senescence in Human Skin Fibroblasts.","authors":"Yuyang Tang, Sen Yang, Zhen Qiu, Li Guan, Yigui Wang, Guixin Li, Yuanyu Tu, Lijuan Guo","doi":"10.1007/s13770-024-00660-2","DOIUrl":"10.1007/s13770-024-00660-2","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress plays an important role in the skin aging process. Rapamycin has been shown to have anti-aging effects, but its role in oxidative senescence of skin cells remains unclear. The aim of this study was to explore the effect of rapamycin on oxidative stress-induced skin cell senescence and to illustrate the mechanism.</p><p><strong>Methods: </strong>Primary human skin fibroblasts (HSFs) were extracted and a model of H<sub>2</sub>O<sub>2</sub>-induced oxidative senescence was constructed, and the effects of rapamycin on their value-added and migratory capacities were detected by CCK-8 and scratch assays. SA-β-gal was utilized to detect senescence, oxidatively closely related factors were also assessed. Gene and protein expressions of senescence, oxidative, and autophagy were detected by western blotting and quantitative-PCR. The data were analyzed by one-way analysis of variance.</p><p><strong>Results: </strong>Rapamycin (0.1 nmol/L for 48 h) promoted the proliferative and migration of H<sub>2</sub>O<sub>2</sub>-treated HSFs (p < 0.05), decreased senescent phenotypes SA-β-gal staining and the expression of P53, and MMP-1 proteins, and increased the expression level of COL1A-1 (p < 0.001). Rapamycin also enhanced the activities of SOD and HO-1, and effectively removed intracellular ROS, MDA levels (p < 0.05), in addition, autophagy-related proteins and genes were significantly elevated after rapamycin pretreatment (p < 0.001). Rapamycin upregulated the autophagy pathway to exert its protective effects.</p><p><strong>Conclusion: </strong>Our findings indicate that rapamycin shields HSFs from H<sub>2</sub>O<sub>2</sub>-induced oxidative damage, the mechanism is related to the reduction of intracellular peroxidation and upregulation of autophagy pathway. Therefore, rapamycin has the potential to be useful in the investigation and prevention of signs of aging and oxidative stress.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1049-1059"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Ji Kim, Ye Jin Song, Tae Gyun Kwon, Jin Ho Lee, So Young Chun, Se Heang Oh
{"title":"Platelet-Rich Plasma-Embedded Porous Polycaprolactone Film with a Large Surface Area for Effective Hemostasis.","authors":"Min Ji Kim, Ye Jin Song, Tae Gyun Kwon, Jin Ho Lee, So Young Chun, Se Heang Oh","doi":"10.1007/s13770-024-00656-y","DOIUrl":"10.1007/s13770-024-00656-y","url":null,"abstract":"<p><strong>Background: </strong>Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives.</p><p><strong>Methods: </strong>We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS).</p><p><strong>Results: </strong>From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself.</p><p><strong>Conclusion: </strong>The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"995-1005"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jung Min Park, Seock Hwan Choi, Eun-Shil Lee, Sang-Il Gum, Sungkuk Hong, Dong Sun Kim, Man-Hoon Han, Soung-Hoon Lee, Ji Won Oh
{"title":"High-Speed Clearing and High-Resolution Staining for Analysis of Various Markers for Neurons and Vessels.","authors":"Jung Min Park, Seock Hwan Choi, Eun-Shil Lee, Sang-Il Gum, Sungkuk Hong, Dong Sun Kim, Man-Hoon Han, Soung-Hoon Lee, Ji Won Oh","doi":"10.1007/s13770-024-00658-w","DOIUrl":"10.1007/s13770-024-00658-w","url":null,"abstract":"<p><strong>Background: </strong>Tissue clearing enables deep imaging in various tissues by increasing the transparency of tissues, but there were limitations of immunostaining of the large-volume tissues such as the whole brain.</p><p><strong>Methods: </strong>Here, we cleared and immune-stained whole mouse brain tissues using a novel clearing technique termed high-speed clearing and high-resolution staining (HCHS). We observed neural structures within the cleared brains using both a confocal microscope and a light-sheet fluorescence microscope (LSFM). The reconstructed 3D images were analyzed using a computational reconstruction algorithm.</p><p><strong>Results: </strong>Various neural structures were well observed in three-dimensional (3D) images of the cleared brains from Gad-green fluorescent protein (GFP) mice and Thy 1-yellow fluorescent protein (YFP) mice. The intrinsic fluorescence signals of both transgenic mice were preserved after HCHS. In addition, large-scale 3D imaging of brains, immune-stained by the HCHS method using a mild detergent-based solution, allowed for the global topological analysis of several neuronal markers such as c-Fos, neuronal nuclear protein (NeuN), Microtubule-associated protein 2 (Map2), Tuj1, glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) in various anatomical regions in the whole mouse brain tissues. Finally, through comparisons with various existing tissue clearing methodologies such as CUBIC, Visikol, and 3DISCO, it was confirmed that the HCHS methodology results in relatively less tissue deformation and higher fluorescence retention.</p><p><strong>Conclusion: </strong>In conclusion, the development of 3D imaging based on novel tissue-clearing techniques (HCHS) will enable detailed spatial analysis of neural and vascular networks present within the brain.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1037-1048"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Se-Young Oh, Ha Yeong Kim, Soo Yeon Jung, Han Su Kim
{"title":"Tissue Engineering and Regenerative Medicine in the Field of Otorhinolaryngology.","authors":"Se-Young Oh, Ha Yeong Kim, Soo Yeon Jung, Han Su Kim","doi":"10.1007/s13770-024-00661-1","DOIUrl":"10.1007/s13770-024-00661-1","url":null,"abstract":"<p><strong>Background: </strong>Otorhinolaryngology is a medical specialty that focuses on the clinical study and treatments of diseases within head and neck regions, specifically including the ear, nose, and throat (ENT), but excluding eyes and brain. These anatomical structures play significant roles in a person's daily life, including eating, speaking as well as facial appearance and expression, thus greatly impacting one's overall satisfaction and quality of life. Consequently, injuries to these regions can significantly impact a person's well-being, leading to extensive research in the field of tissue engineering and regenerative medicine over many years.</p><p><strong>Methods: </strong>This chapter provides an overview of the anatomical characteristics of otorhinolaryngologic tissues and explores the tissue engineering and regenerative medicine research in otology (ear), rhinology (nose), facial bone, larynx, and trachea.</p><p><strong>Results and conclusion: </strong>The integration of tissue engineering and regenerative medicine in otorhinolaryngology holds the promise of broadening the therapeutic choices for a wide range of conditions, ultimately improving quality of a patient's life.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"969-984"},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V E Getova, E Orozco-García, S Palmers, G Krenning, R Narvaez-Sanchez, M C Harmsen
{"title":"Extracellular Vesicles from Adipose Tissue-Derived Stromal Cells Stimulate Angiogenesis in a Scaffold-Dependent Fashion.","authors":"V E Getova, E Orozco-García, S Palmers, G Krenning, R Narvaez-Sanchez, M C Harmsen","doi":"10.1007/s13770-024-00650-4","DOIUrl":"10.1007/s13770-024-00650-4","url":null,"abstract":"<p><strong>Background: </strong>The extracellular vesicles (EVs) secreted by adipose tissue-derived stromal cells (ASC) are microenvironment modulators in tissue regeneration by releasing their molecular cargo, including miRNAs. However, the influence of ASC-derived extracellular vesicles (ASC-EVs) on endothelial cells (ECs) and vascularisation is poorly understood. The present study aimed to determine the pro-angiogenic effects of ASC-EVs and explore their miRNA profile.</p><p><strong>Methods: </strong>EVs were isolated from normoxic and hypoxic cultured ASC conditioned culture medium. The miRNA expression profile was determined by miRseq, and EV markers were determined by Western blot and immunofluorescence staining. The uptake dynamics of fluorescently labelled EVs were monitored for 24 h. ASC-EVs' pro-angiogenic effect was assessed by sprouting ex vivo rat aorta rings in left ventricular-decellularized extracellular matrix (LV dECM) hydrogel or basement membrane hydrogel (Geltrex®).</p><p><strong>Results: </strong>ASC-EVs augmented vascular network formation by aorta rings. The vascular network topology and stability were influenced in a hydrogel scaffold-dependent fashion. The ASC-EVs were enriched for several miRNA families/clusters, including Let-7 and miR-23/27/24. The miRNA-1290 was the highest enriched non-clustered miRNA, accounting for almost 20% of all reads in hypoxia EVs.</p><p><strong>Conclusion: </strong>Our study revealed that ASC-EVs augment in vitro and ex vivo vascularisation, likely due to the enriched pro-angiogenic miRNAs in EVs, particularly miR-1290. Our results show promise for regenerative and revascularisation therapies based on ASC-EV-loaded ECM hydrogels.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"881-895"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junhao Koh, Junqing Liu, Chi Him Poon, Jun Kang, Mohammed S Basabrain, Lee Wei Lim, Chengfei Zhang
{"title":"Transplantation of Neural Progenitor Cells Derived from Stem Cells from Apical Papilla Through Small-Molecule Induction in a Rat Model of Sciatic Nerve Injury.","authors":"Junhao Koh, Junqing Liu, Chi Him Poon, Jun Kang, Mohammed S Basabrain, Lee Wei Lim, Chengfei Zhang","doi":"10.1007/s13770-024-00648-y","DOIUrl":"10.1007/s13770-024-00648-y","url":null,"abstract":"<p><strong>Background: </strong>Stem cell-based transplantation therapy holds promise for peripheral nerve injury treatment, but adult availability is limited. A cell culture protocol utilizing a small-molecule cocktail effectively reprogrammed stem cells from apical papilla (SCAPs) into neural progenitor cells, subsequently differentiating into neuron-like cells. This study aims to evaluate neural-induced SCAPs, with and without small-molecule cocktail, for sciatic nerve repair potential.</p><p><strong>Methods: </strong>A scaffold-free cell sheet technique was used to construct a three-dimensional cell sheet. Subsequently, this cell sheet was carefully rolled into a tube and seamlessly inserted into a collagen conduit, which was then transplanted into a 5 mm sciatic nerve injury rat model. Functional sciatic nerve regeneration was evaluated via toe spread test, walking track analysis and gastrocnemius muscle weight. Additionally, degree of sciatic nerve regeneration was determined based on total amount of myelinated fibers.</p><p><strong>Results: </strong>Small-molecule cocktail induced SCAPs enhanced motor function recovery, evident in improved sciatic function index and gastrocnemius muscle retention. We also observed better host myelinated fiber retention than undifferentiated SCAPs or neural-induced SCAPs without small-molecule cocktail. However, clusters of neuron-like cell bodies (surrounded by sparse myelinated fibers) were found in all cell sheet-implanted groups in the implantation region. This suggests that while the implanted cells likely survived transplantation, integration was poor and would likely hinder long-term recovery by occupying the space needed for host nerve fibers to project through.</p><p><strong>Conclusion: </strong>Neural-induced SCAPs with small-molecule cocktail demonstrated promising benefits for nerve repair; further research is needed to improve its integration and optimize its potential for long-term recovery.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"867-879"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}