Tissue Engineering Part A最新文献

{"title":"The Impact of Vascular Supply on Endochondral Bone Regeneration in Centimeter-Sized Porous Chambers.","authors":"Leanne S de Silva, Casper J Kuijpers, Ellen M Van Cann, Antoine J W P Rosenberg, Robert J J van Es, Debby Gawlitta","doi":"10.1089/ten.tea.2025.0045","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0045","url":null,"abstract":"<p><p>The current clinical treatment of large bone defects in humans primarily relies on autologous bone grafts. However, the use of autologous bone grafts can be limited by tissue availability, variable bone quality, and donor site morbidity. In response to these challenges, endochondral bone regeneration has emerged as a promising approach. This method mimics endochondral ossification by chondrogenically differentiating or stimulating cells of various cell sources into 'callus mimics' (CMs). We previously demonstrated the feasibility of endochondral bone regeneration in restoring bone defects using 'mesenchymal stromal cell' (MSC)-derived devitalized CMs in small and large animals. To scale up the size of treated defects using these CMs, we propose the introduction of a vascular supply. In this study, an arteriovenous (AV) loop was introduced as a vascular supply to devitalized 'MSCs'-derived CMs in a centimeter-scale porous chamber in rats. The extent of vascularization and remodeling was evaluated for chambers filled with CMs in the presence or absence of an AV loop at 4 and 8 weeks. While the AV loop's role in vascularization is established, our study uniquely shows that in a challenging <i>in vivo</i> setting with devitalized callus mimics, the AV loop was critical for initiating bone formation. Mineralization was observed in all groups <i>via</i> microCT, but bone tissue formed only in the AV loop group (50% of samples at 8 weeks), underscoring its influential role in supporting both vascular invasion and bone formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143149","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":"β3GALT2 Gene Promotes Osteogenic Differentiation of BMSCs on n-HA/PA66 Via Exosomes.","authors":"Lipeng Peng, Jian Yang, Linnan Wang, Qiujiang Li, Yueming Song","doi":"10.1089/ten.tea.2025.0013","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0013","url":null,"abstract":"<p><p>While β3GalT2 has been implicated in osteogenic regulation, its synergistic application with bioactive scaffolds remains unexplored. This study pioneers a dual-functional bone regeneration strategy by integrating β3GalT2-engineered bone marrow mesenchymal stem cells (BMSCs-β3GalT2) with nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composites. First, we studied the effect of β3GalT2 on rat BMSCs (rBMSCs) by overexpression the β3GalT2 gene. Following this, we extracted exosomes and verified that β3GalT2 influences osteogenesis of rBMSCs through exosomes. Subsequently, we inoculated these rBMSCs on n-HA/PA66 and demonstrated the effects of β3GalT2 and n-HA/PA66 on osteogenic differentiation of rBMSCs. On this basis, we also explored the molecular mechanism of β3GalT2 regulating M1 polarization through exosomes. Finally, we verified our study by using animal models of skull defect and femur defect. Our results suggest that β3GalT2 promotes osteogenic differentiation of rBMSCs through exosomes. At the same time, rBMSCs-β3GalT2 combined with n-HA/PA66 showed good osteogenic effect <i>in vivo</i> and <i>in vitro</i>. In addition, we also found that β3GalT2 can regulate M1 polarization through exosomes. Our findings establish β3GalT2 as a master regulator of osteogenesis through cellular-exosomal-circuitry mechanisms. The biohybrid system synergistically combines gene-enhanced stem cells with tunable biomaterials, representing a paradigm shift in bone tissue engineering.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144417","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":"Donor Variability and 3D Culture Models Influence Human Mesenchymal Stem Cell Differentiation.","authors":"Sarah Jones, Michelle Tai, Manish Ayushman, Abena Peasah, Julia Johannsen, Fan Yang","doi":"10.1089/ten.tea.2025.0028","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0028","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are widely used for tissue regeneration due to their multilineage differentiation potential and ability to secrete paracrine factors with immunomodulatory and angiogenic functions. Standard MSC differentiation protocols typically rely on two-dimensional (2D) or pellet culture models that are simple to use but not well-suited for translational or clinical applications. To promote better cell survival, tissue deposition, and differentiation of MSCs, a wide variety of three-dimensional (3D) biomaterial scaffolds and platforms have been developed that provide structural support and present a carefully defined set of biochemical and biophysical cues to cells. While biomaterials can guide cell behavior and promote desirable tissue regeneration outcomes, one remaining challenge in the field is inherent donor-to-donor variability in MSC behavior, phenotype, and differentiation capacity. Although MSCs are promising tools for regeneration, the influence of donor variability on MSC differentiation across culture models remains poorly understood. Previous studies typically use cells from a single donor or rely solely on standard culture models. To address these gaps, we compared MSCs from six human donors and assessed differentiation across chondrogenic, osteogenic, and adipogenic lineages using both standard (pellet or 2D) and 3D biomaterial-based culture models. Alginate hydrogels were used to assess chondrogenesis, while gelatin microribbon (µRB) hydrogels were used to evaluate osteogenesis and adipogenesis in 3D. Significant donor-to-donor variability was observed in differentiation outcomes across all three lineages and within both 2D and 3D culture models. By directly comparing donor variability in 2D and 3D, we provide evidence that standard 2D models cannot predict MSC differentiation capacity in 3D biomaterials. Therefore, to improve therapeutic efficacy and advance biomaterial-based strategies for tissue regeneration, it is critical to understand how donor variability affects MSC differentiation patterns across 3D biomaterial-based culture models.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129634","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":"Regenerative Potential of Human Umbilical Cord Vein for Urethral Reconstruction in Male Rabbit Model.","authors":"Clement Parat, Damien Carnicelli, Stephan Langonnet, Marc Sbizzera, Laurence Barnouin, Yao Chen, Laura Barrot, Paul Neuville, Nicolas Morel-Journel","doi":"10.1089/ten.tea.2025.0061","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0061","url":null,"abstract":"<p><p>Tissue engineering offers an alternative for augmentation urethroplasty; however, no ideal material has yet been developed. Recently, materials derived from amniotic tissues appear to exhibit promising properties. Herein, the aim of this study was to provide a proof of concept for the integration of the human umbilical cord vein for urethral reconstructions in rabbits. Rabbits were included in two groups; the control group underwent urethral reconstruction using autograft urethral tissue, and the test group received xenograft tissue (umbilical cord vein) after creating a 1 × 1 cm defect in the proximal urethra. At 3 weeks, endoscopy and biopsy were performed. At 6 weeks, the animals were euthanized, and their urethra and corpus cavernosum were sent for histopathological analysis. The six rabbits exhibited favorable clinical and endoscopic progress with no fistula or stenosis. Biopsy analysis found no lesion of the urothelium and chorion. Final histological analysis found similar results in both groups: normal histology with moderate urothelium vacuolation and a weak inflammatory cellular infiltrate. The present study provides a proof of concept of human umbilical cord vein as a scaffold for urethral regeneration. This could be an alternative to existing urethral tissue grafting procedures that can have difficulties with integration or immunological tolerance; however, further research is required.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129644","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 Novel Injectable Cell-Loaded Hydrogel System for Cartilage Repair: <i>In Vivo</i> and <i>In Vitro</i> Study.","authors":"Beini Mao, Ming Tian, Yuling Yin, Lang Li, Jian Li, Daixu Wei, Weili Fu","doi":"10.1089/ten.tea.2025.0024","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0024","url":null,"abstract":"<p><p>Polyhydroxyalkanoates are promising biomaterials, but their application in cartilage repair is still limited. In this study, an injectable thermosensitive hydrogel poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate)-Polyethylene Glycol (PEG)/hyaluronic acid/kartogenin was prepared from 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, hyaluronic acid, and kartogenin. The hydrogels are porous, temperature-sensitive, and hydrophilic and have good compressive modulus. Mesenchymal stem cells derived from peripheral blood can proliferate on the hydrogels under two- and three-dimensional cultures. In addition, the hydrogel has the ability to induce chondrogenic differentiation of stem cells and induce M2 differentiation of macrophages. The hydrogel loaded with peripheral blood mesenchymal stem cells can repair cartilage defects in the knee joints of New Zealand rabbits and the newly formed cartilage was identified as type II collagen. Overall, this newly developed system could provide a new treatment option for repairing cartilage defects. Impact Statement In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) was modified with hyaluronic acid and kartogenin to synthesize a thermosensitive injectable hydrogel scaffold. The scaffold has anti-inflammatory and cartilage-promoting effects. This study used the scaffold to carry peripheral blood mesenchymal stem cells to repair cartilage defects in rabbit knee joints, providing a new idea for the treatment of cartilage defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027722","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":"Effect of Microbial Stimuli and Bone Morphogenetic Protein 2 on Ectopic Bone Formation.","authors":"Nada Ristya Rahmani, Anneli Duits, Paree Khokhani, Michiel Croes, Vela Kaludjerovic, Debby Gawlitta, Harrie Weinans, Moyo C Kruyt","doi":"10.1089/ten.tea.2025.0020","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0020","url":null,"abstract":"<p><p>Advancements in biomaterials design increasingly focus on material-host immune interactions as one of the strategies to promote new bone formation, referred to as osteoimmunomodulation. Recent studies indicate that inflammatory stimuli can synergize with growth factors such as bone morphogenetic protein 2 (BMP-2) to promote bone formation. Pathogen-associated molecular patterns (PAMPs) are motifs expressed by microbes that are recognized by immune cells and induce an immune-stimulatory response. In this study, we combined PAMPs with low-dose BMP-2 on a biphasic calcium phosphate (BCP) scaffold and evaluated its effect on ectopic bone formation in a subcutaneous implantation model. The PAMPs tested include gamma-irradiated whole microbes (γi-<i>Staphylococcus aureus</i> and γi-<i>Candida albicans</i>), a vaccine (Bacillus Calmette-Guérin containing <i>Mycobacterium bovis</i>), bacterial cell wall components (peptidoglycan [PGN], lipopolysaccharide [LPS], lipoteichoic acid, and Pam3CysSerLys4), an exopolysaccharide (Curdlan), and nucleic acid analogues (polyinosinic:polycytidylic acid [Poly(I:C)] and Cytidine-phosphate-guanosine [CpG]-containing oligonucleotides type C). Implants consisting of BCP, PAMPs, and BMP-2 were placed subcutaneously in rabbits and evaluated for ectopic bone formation after 5 weeks. Implants with only BMP-2 served as controls. Of the PAMPs tested, only PGN and BMP-2 showed a positive bone volume compared with the control, with borderline significance (+4.4%, <i>p</i> = 0.08). Decreased bone volume was seen for LPS (-7.4%, <i>p</i> = 0.03) and Poly(I:C) (-6.3%, <i>p</i> = 0.04). Fluorochrome labeling at weeks 2 and 3 assessed mineralization onset, revealing no mineralization in the first 2 weeks and some implants showing onset at week 3. We observed variability in ectopic bone formation across animals, associated with higher osteoclast numbers in those where ectopic bone occurred versus those that did not (<i>p</i> = 0.004). PAMPs can modulate bone formation, but their effects are variable, requiring further refinement to harness their osteoimmunomodulatory properties effectively. Additionally, we highlight osteoclasts' important role in stimulating ectopic bone formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043435","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>In Situ</i> Bioprinting Embryonic-Derived Stem Cells to Repair Human <i>Ex Vivo</i> Chondral Defects.","authors":"Shawn P Grogan, Erik W Dorthé, Nicholas E Glembotski, Darryl D D'Lima","doi":"10.1089/ten.tea.2024.0346","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0346","url":null,"abstract":"<p><p>Successful bioprinting requires an appropriate combination of bioinks, cells, and a delivery platform. To demonstrate the potential of <i>in situ</i> bioprinting for regeneration of cartilage lesions we combined clinically relevant embryonic-derived mesenchymal stem cells (ES-MSCs) with a fibrin-based bioink that was delivered into chondral defects created in human <i>ex vivo</i> osteoarthritic (OA) tissue using a bioprinting platform. We used an integrated multitool, 6-axis bioprinting system to laser scan and map the surface of chondral defects and bioprint within the cartilage defects <i>in vitro</i> and <i>ex vivo</i>. For cartilage neotissue generation, clinically relevant ES-MSCs were encapsulated at 20 × 10⁶ cells per mL in chondro-inductive bioinks composed of fibrinogen mixed with nanocellulose or fibrinogen mixed with nanocellulose and hyaluronic acid. After bioprinting as free-standing constructs or <i>in situ</i> within chondral defects, gels were cross-linked in thrombin and cultured for up to 8 weeks in chondrogenic medium. Print fidelity was assessed in the free-standing printed constructs after cross-linking and culture. <i>In situ</i> bioprinted constructs were evaluated for cell viability, mechanical properties, histology (Safranin O and collagen type II immunostaining), and gene expression of chondrogenic genes. Adding nanocellulose to fibrinogen significantly improved print fidelity. ES-MSCs in the fibrinogen-based bioink formulations generated cartilage-like neotissues with positive Safranin O and collagen type II staining. Chondrogenic genes (COLA2A1, ACAN, COMP, and SOX9) were significantly upregulated with negligible expression of hypertrophic markers (COL10A1 and RUNX2). The mechanical properties of the printed constructs increased from 30 to 50 kPa after 3 weeks to ∼150 kPa after 8 weeks in culture. We demonstrated the feasibility of combining clinically relevant ES-MSCs with printable fibrin-based hydrogel bioinks and an integrated bioprinting platform for <i>in situ</i> bioprinting that promoted neocartilage tissue generation and repair of <i>ex vivo</i> lesions in human OA tissues.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021314","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":"Glycations on Decellularized Muscle Matrix Reduce Muscle Regeneration and Increase Inflammation.","authors":"Lucas C Olson, Ammar Y Jawad, Eirian S Crocker, Scott E Pennebaker, Brock P Lodato, David J Cohen, Zvi Schwartz, Michael J McClure","doi":"10.1089/ten.tea.2024.0284","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0284","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) due to traumatic injury results in the abrupt loss of contractile units, stem cells, and connective tissue, leading to long-term muscle dysfunction and reduced regenerative potential. Muscle connective tissue contains a proregenerative extracellular matrix (ECM), and our lab harnesses the regenerative capacity of decellularized muscle matrix (DMM) to treat VML, a condition with limited treatment options. However, a major limitation is that muscle often comes from aged donors. Previous work from our lab showed that aged donor muscle contains higher levels of advanced glycation end-product (AGE) cross-links compared to muscle from younger donors. This study aimed to determine whether increased AGE cross-links reduce the regenerative capacity of DMM. To test this, we first generated AGEs in DMM with direct D-ribose incubation. We then removed ∼35% of the gastrocnemius muscle in a model and treated it with either AGE-DMM or standard DMM (no AGEs), comparing results to controls. Although muscle force results remained unchanged between AGE-DMM and DMM, AGEs led to reduced muscle mass in histological sections, fewer fibers, and smaller fiber diameters. AGEs also increased collagen levels in histology, but protein assays showed reduced collagen production. We investigated the canonical receptor for AGEs, the receptor for AGEs (RAGE), and found elevated levels in AGE-treated VML compared to DMM alone, along with increased levels of the noncanonical receptor galectin-3. Both RAGE and galectin-3 are associated with inflammation, and proteomics revealed higher inflammatory markers in AGE-treated muscle than in DMM alone. In conclusion, our data suggest that AGEs impair the regenerative potential of DMM, highlighting the importance of considering donor age when sourcing muscle for DMM therapies. Impact Statement This study investigates advanced glycation end-product cross-links in skeletal muscle extracellular matrix (ECM) as a way to model its deleterious effects on muscle regeneration <i>in vivo</i>. We demonstrate here that ECM glycations reduce muscle regeneration, enhance inflammatory markers, reduce ECM protein production, and proteomic analysis identified unique targets that could be explored in future research endeavors.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993368","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":"An Infection Model for SARS-CoV-2 Using Rat Transplanted with hiPSC-Airway Epithelial Cells.","authors":"Masayuki Kitano, Hiroe Ohnishi, Akiko Makino, Tatsuo Miyamoto, Yasuyuki Hayashi, Keisuke Mizuno, Shinji Kaba, Yoshitaka Kawai, Tsuyoshi Kojima, Yo Kishimoto, Norio Yamamoto, Keizo Tomonaga, Koichi Omori","doi":"10.1089/ten.TEA.2024.0016","DOIUrl":"10.1089/ten.TEA.2024.0016","url":null,"abstract":"<p><p>Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various <i>in vitro</i> models, such as cell lines and primary cultures, and <i>in vivo</i> models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the <i>GFP</i> gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"361-372"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238790","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":"Rat Tracheal Cartilage Regeneration Using Mesenchymal Stem Cells Derived From Human iPS Cells.","authors":"Keisuke Mizuno, Hiroe Ohnishi, Yo Kishimoto, Tsuyoshi Kojima, Shintaro Fujimura, Yoshitaka Kawai, Masayuki Kitano, Makoto Ikeya, Koichi Omori","doi":"10.1089/ten.TEA.2024.0151","DOIUrl":"10.1089/ten.TEA.2024.0151","url":null,"abstract":"<p><p>Tracheal cartilage provides structural support to the airways to enable breathing. However, it can become damaged or impaired, sometimes requiring surgical resection and reconstruction. Previously, we clinically applied an artificial trachea composed of a polypropylene mesh and collagen sponge, with a favorable postoperative course. However, the artificial trachea presents a limitation, as the mesh is not biodegradable and cannot be used in pediatric patients. Compared to a polypropylene mesh, regenerated cartilage represents an ideal material for reconstruction of the damaged trachea. The use of mesenchymal stem cells (MSCs) as a source for cartilage regeneration has gained widespread acceptance, but challenges such as the invasiveness of harvesting and limited cell supply persist. Therefore, we focused on the potential of human-induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) for tracheal cartilage regeneration. In this study, we aimed to regenerate tracheal cartilage on an artificial trachea as a preliminary step to replace the polypropylene mesh. iMSCs were induced from hiPSCs through neural crest cells and transplanted with a polypropylene mesh covered with a collagen sponge into the damaged tracheal cartilage in immunodeficient rats. Human nuclear antigen (HNA)-positive cells were observed in all six rats at 4 weeks and in six out of seven rats at 12 weeks after transplantation, indicating that transplanted iMSCs survived within the tracheal cartilage defects of rats. The HNA-positive cells coexpressed SOX9, and type II collagen was detected around HNA-positive cells in four of six rats at 4 weeks and in three of seven rats at 12 weeks after transplantation, reflecting cartilage-like tissue regeneration. These results indicate that the transplanted iMSCs could differentiate into chondrogenic cells and promote tracheal cartilage regeneration. iMSC transplantation thus represents a promising approach for human tracheal reconstruction.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"398-408"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545582","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}