Jingjing Shao, Shibo Liu, Chenfeng Chen, Wenchuan Chen, Zhimin Zhu, Lei Li
{"title":"Aging Impairs Implant Osseointegration Through a Novel Reactive Oxygen Species-Hypoxia-Inducible Factor 1α/p53 Axis.","authors":"Jingjing Shao, Shibo Liu, Chenfeng Chen, Wenchuan Chen, Zhimin Zhu, Lei Li","doi":"10.1089/ten.tea.2024.0355","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0355","url":null,"abstract":"<p><p>Enhancing bone-vessel coupling to form high-quality vascular-rich peri-implant bone is crucial for improving implant prognosis in elder patients. Notably, hypoxia-inducible factor 1α (HIF1α) is known to promote osteogenesis-angiogenesis coupling; however, this effect remains to be investigated in aged bone owing to the dual effect of HIF1α in different aged organs. In this study, HIF1α inhibitor or activator was applied to aged mice and their bone mesenchymal stem cells (BMSCs) to investigate the effects and inner mechanism of HIF1α on the peri-implant osteogenesis and angiogenesis in senescent status. Cell senescence, along with osteogenic and angiogenic abilities of aged BMSCs, was detected, respectively. Meanwhile, a femur implant implantation model was constructed on aged mice, and the bone-vessel coupling of peri-implant bone was observed. Mandibular bone morphology was also detected to further provide evidence for clinical oral implantation. Furthermore, p53 expression was examined <i>in vivo</i> and <i>in vitro</i> following HIF1α intervention. A reactive oxygen species (ROS) scavenger was also adopted to further investigate the roles of ROS in the HIF1α-p53 axis. Results showed that the suppression of HIF1α alleviated senescence and osteogenesis-angiogenesis coupling of aged BMSCs, while its activation aggravated these effects. The mandible phenotype and bone-vessel coupling in aged peri-implant bone also changed accordingly upon regulation of HIF1α. Mechanistically, p53 changed in the same direction as HIF1α <i>in vivo</i> and <i>in vitro</i>. Moreover, the ROS scavenger reversed the HIF1α-p53 relationship and weakened the effect of HIF1α inhibitor on peri-implant bone improvement. In conclusion, in aged mice, highly expressed HIF1α impaired peri-implant bone-vessel coupling and implant osseointegration through p53, and accumulated ROS was a prerequisite for HIF1α to positively regulate p53. These findings provide new insights into the role of HIF1α and the ROS-HIF1α/p53 signaling axis, offering potential therapeutic targets to improve implant outcomes in elderly patients.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765905","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}
Qiang Zhu, Zhezheng Chen, Ting Fu, Ya Lin, Xiaorong Lan, Jingang Xiao, Lin Liu
{"title":"ZC3H13 Regulates Ferroptosis to Enhance Osteogenic Differentiation in Osteoporotic BMSCs.","authors":"Qiang Zhu, Zhezheng Chen, Ting Fu, Ya Lin, Xiaorong Lan, Jingang Xiao, Lin Liu","doi":"10.1089/ten.tea.2024.0243","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0243","url":null,"abstract":"<p><p><b><i>Objectives:</i></b> N6-methyladenosine (m<sup>6</sup>A) modification is critical in the regulation of osteoporosis (OP). Although ZC3H13 is an important m<sup>6</sup>A methyltransferase, its specific regulatory effects and mechanisms in osteoporosis are not yet fully understood. Therefore, we investigated the impact of ZC3H13 on the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) in osteoporosis and attempted to elucidate its underlying mechanism. <b><i>Materials and Methods:</i></b> Western blotting, quantitative reverse transcription polymerase chain reaction, and immunohistochemical staining were used to identify changes in ZC3H13 and osteogenic factor (RUNX2 and OPN) expression in osteoporosis. Gain- and loss-of-function experiments were conducted to study the impact of ZC3H13 on the osteogenic differentiation of osteoporotic BMSCs (OP-BMSCs). Transcriptomic sequencing, transmission electron microscopy, and intraperitoneal injection of the ferroptosis inhibitor ferrostatin-1 (Fer-1) were used to elucidate the downstream mechanisms regulated by ZC3H13 in osteoporosis. In addition, rescue assays were performed to elucidate the underlying molecular mechanisms involved. <b><i>Results:</i></b> Here, we revealed that ZC3H13 was downregulated in OP-BMSCs and osteoporotic rat femurs, which correlated with the reduced osteogenic differentiation of OP-BMSCs. Functionally, ZC3H13 knockdown resulted in decreased osteogenic differentiation of the BMSCs, whereas ZC3H13 overexpression promoted the osteogenic differentiation of the OP-BMSCs. Furthermore, ZC3H13 knockdown was closely related to metal ion binding, reduced cell proliferation, and altered mitochondrial morphology. Treatment with the ferroptosis inhibitor Fer-1 partially reversed osteoporotic phenotypes <i>in vivo</i>. Mechanistically, ZC3H13 was shown to promote osteogenic differentiation in OP-BMSCs by inhibiting ferroptosis. <b><i>Conclusions:</i></b> Our study revealed that ZC3H13 promoted the osteogenic differentiation of BMSCs by inhibiting ferroptosis in osteoporosis. This research offers a reliable theoretical foundation for predicting and treating osteoporosis.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702392","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}
Markus Laubach, Stephen Whyte, Ho Fai Chan, Frank Hildebrand, Boris M Holzapfel, Ulrich Kneser, Uwe Dulleck, Dietmar W Hutmacher
{"title":"How Framing Bias Impacts Preferences for Innovation in Bone Tissue Engineering.","authors":"Markus Laubach, Stephen Whyte, Ho Fai Chan, Frank Hildebrand, Boris M Holzapfel, Ulrich Kneser, Uwe Dulleck, Dietmar W Hutmacher","doi":"10.1089/ten.TEA.2023.0338","DOIUrl":"10.1089/ten.TEA.2023.0338","url":null,"abstract":"<p><p>It is currently unknown if surgeons and biomaterial scientists &or tissue engineers (BS&orTE) process and evaluate information in similar or different (un)biased ways. For the gold standard of surgery to move \"from bench to bedside,\" there must naturally be synergies between these key stakeholders' perspectives. Because only a small number of biomaterials and tissue engineering innovations have been translated into the clinic today, we hypothesized that this lack of translation is rooted in the psychology of surgeons and BS&orTE. Presently, both clinicians and researchers doubt the compatibility of surgery and research in their daily routines. This has led to the use of a metaphorical expression \"squaring of the circle,\" which implies an unsolvable challenge. As bone tissue engineering belongs to the top five research areas in tissue engineering, we choose the field of bone defect treatment options for our bias study. Our study uses an online survey instrument for data capture such as incorporating a behavioral economics cognitive framing experiment methodology. Our study sample consisted of surgeons (<i>n</i> = 208) and BS&orTE (<i>n</i> = 59). And we used a convenience sampling method, with participants (conference attendants) being approached both in person and through email between October 22, 2022, and March 13, 2023. We find no distinct positive-negative cognitive framing differences by occupation. That is, any framing bias present in this surgical decision-making setting does not appear to differ significantly between surgeon and BS&orTE specialization. When we explored within-group differences by frames, we see statistically significant (<i>p</i> < 0.05) results for surgeons in the positive frame ranking autologous bone graft transplantation lower than surgeons in the negative frame. Furthermore, surgeons in the positive frame rank Ilizarov bone transport method higher than surgeons in the negative frame (<i>p</i> < 0.05).</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"277-283"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961286","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}
Ching-Wen Tsai, Tzung-Yu Chen, Jyh-Horng Wang, Tai-Horng Young
{"title":"Effect of Chitosan on Synovial Membrane Derived Cells and Anterior Cruciate Ligament Fibroblasts.","authors":"Ching-Wen Tsai, Tzung-Yu Chen, Jyh-Horng Wang, Tai-Horng Young","doi":"10.1089/ten.TEA.2024.0077","DOIUrl":"10.1089/ten.TEA.2024.0077","url":null,"abstract":"<p><p>Previously, chitosan reduces the senescence-related phenotypes in human foreskin fibroblasts through the transforming growth factor beta (TGF-β) pathway, and enhances the proliferation and migration capabilities of these cells are demonstrated. In this study, we examined whether the senescence-delaying effect of chitosan could be applied to primary knee-related fibroblasts, such as human synovial membrane derived cells (SCs) and anterior cruciate ligament fibroblasts (ACLs). These two types of cells were obtained from donors who needed ACL reconstruction or knee replacement. We found that chitosan treatment effectively reduced aging-associated β-galactosidase (SA-β-gal)-positive cells, downregulated the expression of senescence-related proteins pRB and p53, and enhanced the 5-bromo-2'-deoxyuridine (BrdU) incorporation ability of SCs and ACLs. Moreover, chitosan could make SCs secret more glycosaminoglycans (GAGs) and produce type I collagen. The ability of ACLs to close the wound was also enhanced, and the TGF-β and alpha smooth muscle actin (αSMA) protein expression decreased after chitosan treatment. In summary, chitosan not only delayed the senescence but also enhanced the functions of SCs and ACLs, which is beneficial to the application of chitosan in cell expansion <i>in vitro</i> and cell therapy.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"267-276"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872101","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}
Haotian Han, Zhihua Zhou, Ting Shang, Shuaijun Li, Xiang Shen, Jianjun Fang, Lei Cui
{"title":"Silk Fibroin-Laponite Porous Microspheres as Cell Microcarriers for Osteogenic Differentiation.","authors":"Haotian Han, Zhihua Zhou, Ting Shang, Shuaijun Li, Xiang Shen, Jianjun Fang, Lei Cui","doi":"10.1089/ten.TEA.2024.0070","DOIUrl":"10.1089/ten.TEA.2024.0070","url":null,"abstract":"<p><p>Silk fibroin (SF) has garnered significant attention as a natural polymer for fabricating porous scaffolds in various engineering applications. However, the limited osteoinductive property of SF has hindered its efficacy in bone repair applications. In this study, we constructed an SF-based injectable porous microcarrier that is doped with laponite (LAP), containing magnesium ions (Mg<sup>2+</sup>). The influence of freezing temperatures and concentrations of SF and LAP on the structural parameters of SF-LAP microcarriers was investigated. The SF-LAP microcarrier exhibited a porosity of 76.7 ± 1.2% and a controlled pore size of 24.6 ± 4.0 μm. At the 6 weeks of <i>in vitro</i> degradation test, a mild alkaline level in culture medium containing SF-LAP microcarriers was detected. The release of Mg<sup>2+</sup> from the SF-LAP microcarrier was maintained at a concentration within the range of 1.2-2.3 mM during the 6 weeks. The seeded human adipose-derived stem cells in the SF-LAP microcarrier demonstrated a significant enhancement in osteogenic differentiation compared with cells seeded in the pure SF microcarrier, as evidenced by quantitative alkaline phosphatase activity and the expression of osteogenic marker genes. These findings underscore the potential of the SF-LAP microcarrier as an ideal cell carrier in the treatment of bone defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"255-266"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870468","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":"A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances <i>In Vivo</i> Cartilage Regeneration.","authors":"Jiaming Zhao, Zexing Yan, Yufei Ding, Yike Dai, Ziyang Feng, Zhiyao Li, Lifeng Ma, Naicheng Diao, Ai Guo, Heyong Yin","doi":"10.1089/ten.TEA.2023.0344","DOIUrl":"10.1089/ten.TEA.2023.0344","url":null,"abstract":"<p><p>Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility <i>in vitro</i>, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, <i>in vivo</i> experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"219-233"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337849","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}
Vanessa Muth, Felix Strobl, Julian Michelotto, Linda Gilles, Jennifer A Kirwan, Alina Eisenberger, Jeremy Marchand, Nathalie N Roschke, Simon Moosburner, Johann Pratschke, Igor M Sauer, Nathanael Raschzok, Joseph M G V Gassner
{"title":"Quality Assessment by Bile Composition in Normothermic Machine Perfusion of Rat Livers.","authors":"Vanessa Muth, Felix Strobl, Julian Michelotto, Linda Gilles, Jennifer A Kirwan, Alina Eisenberger, Jeremy Marchand, Nathalie N Roschke, Simon Moosburner, Johann Pratschke, Igor M Sauer, Nathanael Raschzok, Joseph M G V Gassner","doi":"10.1089/ten.TEA.2024.0048","DOIUrl":"10.1089/ten.TEA.2024.0048","url":null,"abstract":"<p><p><b><i>Background:</i></b> The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked <i>in vivo</i> conditions during normothermic machine perfusion, the liver is metabolically active, which allows quality assessment during perfusion. Bile seems to be of rising interest in clinical studies, as it is easily collectible for analysis. As there are currently no data on biliary bile acids during NMP, the primary objective of this study was to use our experimental rodent NMP model to assess changes in bile composition through organ damage during perfusion to inform clinical evaluation of donor organs during NMP. <b><i>Methods:</i></b> Thirty livers from male Sprague-Dawley rats in five groups underwent 6 h of NMP using either erythrocyte-supplemented DMEM or Steen solution, with or without 30 min of warm ischemia time (WIT). We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at 3-hour intervals. Bile samples were analyzed for biliary pH, LDH, and gamma glutamyltransferase, as well as biliary bile acids via mass spectrometry and UHPLC. <b><i>Results:</i></b> Compared with regular livers, liver injury parameters were significantly higher in our donation after circulatory death (DCD) model. Bile production was significantly reduced in livers exposed to WIT, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers experiencing WIT. However, regular livers produced a higher total amount of biliary bile acids during perfusion. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced during perfusion due to the missing enterohepatic circulation. <b><i>Conclusions:</i></b> WIT-induced liver injury affects bile composition within our small-animal NMP model. We hypothesize this phenomenon to be attributed to the energy-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile. Our results may inform clinical studies, in which biliary bile acids might have a potential as a quantifiable viability marker in human NMP liver transplantation studies.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"244-254"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238842","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}
Simon Andreas Mayer, Benjamin Thomas, Miriam Heuer, Jan C Brune, Volker Eras, Kilian Schuster, Leonard Knoedler, Rebecca Luisa Schaefer, Wilko Thiele, Jonathan P Sleeman, Arno Dimmler, Patrick Heimel, Ulrich Kneser, Amir K Bigdeli, Florian Falkner
{"title":"<i>In Vivo</i> Engineering and Transplantation of Axially Vascularized and Epithelialized Flaps in Rats.","authors":"Simon Andreas Mayer, Benjamin Thomas, Miriam Heuer, Jan C Brune, Volker Eras, Kilian Schuster, Leonard Knoedler, Rebecca Luisa Schaefer, Wilko Thiele, Jonathan P Sleeman, Arno Dimmler, Patrick Heimel, Ulrich Kneser, Amir K Bigdeli, Florian Falkner","doi":"10.1089/ten.TEA.2024.0037","DOIUrl":"10.1089/ten.TEA.2024.0037","url":null,"abstract":"<p><p>The arteriovenous loop (AVL) model allows the <i>in vivo</i> engineering of axially vascularized flaps, the so-called AVL flaps. Although AVL flaps can be transplanted microsurgically to cover tissue defects, they lack an epithelial layer on the surface. Therefore, the objective of this study was to engineer axially vascularized AVL flaps with an accompanying epithelial layer for local defect reconstruction. In this study, AVLs were established in 20 male Lewis rats. Minimally invasive injection of keratinocytes onto the surface of the AVL flaps was performed on postoperative day (POD) 21. AVL flaps were explanted from 12 rats on POD 24 or POD 30, then the epithelium formed by the keratinocytes on the surface of the flaps was evaluated using immunofluorescence staining. In six other rats, the AVL flap was locally transposed to cover a critical defect in the rats' leg on POD 30 and explanted for analysis on POD 40. In two control rats, sodium chloride was applied instead of keratinocytes. These control flaps were also transplanted on POD 30 and explanted on POD 40. Our results revealed that 3 days after keratinocyte application, a loose single-layered epithelium was observed histologically on the AVL flaps surface, whereas after 9 days, a multilayered and structured epithelium had grown. The epithelium on the transplanted AVL flaps showed its physiological differentiation when being exposed to an air-liquid interface. Histologically, a layered epithelium identical to the rats' regular skin was formed. In the sodium chloride control group, no epithelium had been grown. This study clearly demonstrates that axially vascularized AVL flaps can be processed in the subcutaneous chamber by minimally invasive injection of keratinocytes. Thus, AVL flaps with an intact epithelial layer were engineered and could be successfully transplanted for local defect coverage in a small animal model.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"234-243"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874050","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}
Alexandra D Avera, Daniel J Gibson, Macy L Birge, Taylor N Schnorbus, Isabella M Concannon, Yonghyun Kim
{"title":"Characterization of Native Extracellular Matrix of Patient-Derived Glioblastoma Multiforme Organoids.","authors":"Alexandra D Avera, Daniel J Gibson, Macy L Birge, Taylor N Schnorbus, Isabella M Concannon, Yonghyun Kim","doi":"10.1089/ten.tea.2024.0303","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0303","url":null,"abstract":"<p><p>Model systems play a crucial role in biological and biomedical research, especially in the search for new treatments for challenging diseases such as glioblastoma multiforme (GBM). Organoids are 3D <i>in vitro</i> multicellular \"middle-ground\" model systems that recapitulate highly organized and heterogeneous <i>in vivo</i> organ-like systems, often through stem cell differentiation. Incorporating Matrigel™ or other exogenous extracellular matrices (ECMs) that do not naturally occur in the human body is common practice for organoid generation, ignoring the role of dynamic reciprocity between the cells and the ECM in tissue development. In this study, we describe a method to develop GBM organoids (GBOs) from cells without the need for exogenous ECM encapsulation and without cell culture media changes to produce stable tissue-like organoids that reach a 4 mm diameter in as little as 6 weeks. We observed a transition from homogenous cell populations to tissue-like structures when GBOs were larger than 1 mm in diameter. Transcriptomic analysis revealed that the greatest gene expression changes occurred when GBOs were 2 mm in diameter, with collagen VI as the most upregulated ECM-related gene. Quantitative and histochemical assessments further supported native ECM synthesis with significantly higher levels of glycosaminoglycans and collagen in GBOs compared with spheroids. To our knowledge, this study presents the first reproducibly large GBOs with natively produced ECMs. Organoids with natively synthesized ECMs promise to eliminate artifacts and variability from aged, homogeneic, or xenogeneic scaffolds and to provide insights for ECM-targeted drug development.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450957","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}
Venkateswaran Ganesh, Rui He, Henry L Keen, Aliasger K Salem, Edward A Sander, Kyungsup Shin, James A Martin, Dongrim Seol
{"title":"Profiles of Exosomal microRNAs in Joint Cells and Candidate microRNAs for Cartilage Regeneration.","authors":"Venkateswaran Ganesh, Rui He, Henry L Keen, Aliasger K Salem, Edward A Sander, Kyungsup Shin, James A Martin, Dongrim Seol","doi":"10.1089/ten.tea.2024.0299","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0299","url":null,"abstract":"<p><p>The activation of chondrogenic progenitor cells (CPCs) in articular cartilage during a traumatic injury is vital for cartilage regeneration. Although our understanding of the mechanisms underlying CPC chondrogenic activation remains incomplete, there is evidence that exosomal microRNAs (miRNAs or miRs) are involved in tissue healing due to their regulating role of posttranscriptional gene expressions. In this study, we profiled enriched and differential expression of miRNAs in exosomes derived from bovine joint cells (CPCs, chondrocytes, and synoviocytes) via Next Generation Sequencing analysis and validated the potential therapeutic effects of candidate exosomal miRNAs for cartilage regeneration. For CPC-based cartilage regeneration, we tested the impact of administering miR-107, miR-140, and miR-148a on CPCs because we found that these miRNAs were highly and differentially expressed in chondrocytes-derived exosomes (CC-Exo). We found that: (1) miR-140 induced chondrogenic gene expression including SRY-box transcription factor 9, collagen type 2A1, and aggrecan, and (2) miR-107 suppressed catabolic gene expression including matrix metalloproteinase 3, a disintegrin and metalloproteinase with thrombospondin motifs 5, and nitric oxide synthase 2. Our findings indicate that transfection of CPCs with specific chondrogenic miRNAs present in CC-Exo have the potential to promote CPC-based cartilage regeneration and could be an important component of posttraumatic osteoarthritis prevention.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416332","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}