Jeong Eun Kim, Ji Yeong Noh, Kyeong Eun Lee, Young Il Lee, Juyun Park, Min Chan Kim, Da Hyeon Choi, Hye Ji Jung, Hee Sung Jung, Jung Won Park, Eun-Ok Lee, Van Thi Lo, Hye Kwon Kim, Yoon Shin Park
{"title":"Non-Cytopathic Mammalian Orthoreovirus Infection Triggers Innate Immune Responses in Human Tonsil-Derived Mesenchymal Stem Cells: Implications for Cell Therapy Quality Control.","authors":"Jeong Eun Kim, Ji Yeong Noh, Kyeong Eun Lee, Young Il Lee, Juyun Park, Min Chan Kim, Da Hyeon Choi, Hye Ji Jung, Hee Sung Jung, Jung Won Park, Eun-Ok Lee, Van Thi Lo, Hye Kwon Kim, Yoon Shin Park","doi":"10.1007/s13770-026-00825-1","DOIUrl":"10.1007/s13770-026-00825-1","url":null,"abstract":"<p><strong>Background: </strong>Tonsil-derived mesenchymal stem cells (TMSCs) are widely used in regenerative medicine due to their high proliferative capacity and differentiation potential. However, their origin from immunological gateways exposes them to pathogens, raising concern about viral contamination during cell preparation. Understanding how these pathogens affect the biological and immunological properties of TMSCs is crucial for ensuring the safety and consistency of cell-based therapies. This study evaluated TMSC susceptibility and molecular responses to mammalian orthoreovirus (MRV).</p><p><strong>Methods: </strong>MRV infectivity in TMSCs and the innate immune responses were investigated using RNA-seq. Viral replication was confirmed by viral titration, L1 segment RT-PCR, and transcriptome mapping. Cellular impact was assessed using Live/Dead assays and protein-protein interaction network analysis.</p><p><strong>Results: </strong>TMSCs were infected with MRV strains to evaluate their susceptibility. Although no significant cytopathic effects were observed, the cells exhibited high viral permissivity to MRV, with stable viral titers of 3.9-5.5 log TCID<sub>50</sub>/ml and positive L1 gene segment RT-PCR. RNA-seq confirmed active replication, with reads successfully mapped to the MRV genome. Transcriptomic profiling showed robust induction of antiviral and stress response genes, including HSPA6, PEG10, OASL, and IFIT2. Gene set enrichment and protein network analyses highlighted enrichment of viral defense pathways and identified IL1B, ISG15, and RSAD2 as key hub genes driving the host inflammatory immune response.</p><p><strong>Conclusion: </strong>MRV establishes a permissive but non-cytopathic infection in TMSCs, triggering innate immune activation through upregulation of IL1B, ISG15, and RSAD2. This virus-induced shift from a quiescent to an immunomodulatory phenotype may compromise therapeutic consistency. Because visual quality control fails to detect latent infections, rigorous viral monitoring during TMSC preparation is essential to ensure safety in clinical applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"917-931"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472774","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":"In-Depth Analysis of AG73-Dental Pulp Cell Interactions Underlying Adhesion and Mineralization: Insights from Alanine Scanning.","authors":"Jia Tang, Akimi Muramatsu, Youjing Qiu","doi":"10.1007/s13770-026-00815-3","DOIUrl":"10.1007/s13770-026-00815-3","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore the dental applications of AG73, a laminin-derived adhesive peptide, by examining its effects on human dental pulp cells (hDPCs), particularly in cell adhesion and mineralization. It also sought to identify the key functional residue of AG73 and the signaling pathways involved in its pro-mineralization activity.</p><p><strong>Methods: </strong>We compared AG73's pro-mineralization activity with peptides derived from LAMA5 using alizarin red staining. Immunofluorescence staining assessed its cell adhesion properties. Alanine-scanning mutagenesis was performed to identify key residues for AG73's adhesion activity. Finally, we used p38 and JNK MAPK inhibitors to determine which signaling pathways were involved in AG73-induced mineralization.</p><p><strong>Results: </strong>AG73 exhibited superior pro-mineralization activity compared to other peptides derived from LAMA5 in hDPCs. Immunofluorescence staining confirmed AG73's strong cell adhesive ability within 20 minutes. Alanine-scanning identified isoleucine at the tenth position as crucial for adhesion. AG73 was the most effective peptide in inducing mineralization, with no mutated versions outperforming it. p38 signaling was found to play a positive role in AG73-induced mineralization, while JNK inhibition enhanced mineralization, suggesting JNK inhibitors as potential inducers.</p><p><strong>Conclusion: </strong>AG73 has strong pro-mineralization activity and significant cell adhesive properties in hDPCs. The isoleucine at the tenth amino acid position was identified as a critical residue for AG73's adhesive ability. Additionally, p38 was found to be involved in AG73-regulated mineralization, while JNK inhibition promoted the process. This is the first study to explore AG73's effects in hDPCs and provides a foundation for its potential use as a dental-pulp regenerative material.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"851-865"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362579","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}
Harry Jung, Hyeonsun Kim, Jihyeon Lee, Hyeon Gyeong Kim, Jae Jun Lee, Kyunghyuk Park, Bukyoung Cha, Sang Hyen Yu, Minji Kim, Sun-Wha Im, Ok Joo Lee, Hae Sang Park
{"title":"Differential Wound Healing Potential of Tonsil Parenchymal and Epithelial Mesenchymal Stromal Cell-Derived Exosomes.","authors":"Harry Jung, Hyeonsun Kim, Jihyeon Lee, Hyeon Gyeong Kim, Jae Jun Lee, Kyunghyuk Park, Bukyoung Cha, Sang Hyen Yu, Minji Kim, Sun-Wha Im, Ok Joo Lee, Hae Sang Park","doi":"10.1007/s13770-026-00818-0","DOIUrl":"10.1007/s13770-026-00818-0","url":null,"abstract":"<p><strong>Background: </strong>The biological characteristics of mesenchymal stromal cells (MSCs) and their exosomes can vary depending on the tissue layer of origin, potentially influencing their regenerative capacity. This study aimed to determine whether exosomes derived from epithelial (TE-MSCs) and parenchymal (TP-MSCs) layers of human tonsils exhibit distinct therapeutic effects in oral mucositis (OM).</p><p><strong>Methods: </strong>MSCs Were isolated from the epithelial (TE-MSCs) and parenchymal (TP-MSCs) layers of human tonsils. Exosomes were characterized and tested for regenerative and anti-inflammatory effects in vitro and in a 5-FU-induced OM hamster model RESULTS: Both TP-MSCs and TE-MSCs exhibited typical MSC phenotypes and multipotency comparable to BMSCs. Transcriptomic profiling revealed distinct layer-specific features, with TE-MSCs enriched in developmental and morphogenetic pathways. TE-MSC-derived exosomes (TE-MSC-Exo) showed enhanced wound closure, downregulation of IL-1β and TNF-α, and selective induction of HGF and ICAM-1 expression. In vivo, TE-MSC-Exo treatment resulted in the smallest mean wound size and most complete re-epithelialization among experimental groups.</p><p><strong>Conclusion: </strong>Exosomes derived from tonsil MSCs effectively promote epithelial regeneration in OM, with TE-MSC-Exo exhibiting enhanced therapeutic potential. These findings highlight the importance of MSC layer origin in defining exosome function and suggest that TE-MSC-Exo may serve as a promising platform for exosome-based mucosal repair therapies.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"833-850"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206172","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}
Kkotnara Park, Areum Cho, Jung Min Park, Mee Sook Jun, Eunbi Ko, Soon-Sun Bak, Jung Min Suh, Kyoungmi Kim, Young Kwan Sung, Daekee Lee, Yun Soo Bae, Ji Won Oh
{"title":"GPRC6A-Duox1 Axis Regulates the Hair Cycle Through H<sub>2</sub>O<sub>2</sub> Generation.","authors":"Kkotnara Park, Areum Cho, Jung Min Park, Mee Sook Jun, Eunbi Ko, Soon-Sun Bak, Jung Min Suh, Kyoungmi Kim, Young Kwan Sung, Daekee Lee, Yun Soo Bae, Ji Won Oh","doi":"10.1007/s13770-026-00807-3","DOIUrl":"10.1007/s13770-026-00807-3","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that G-protein-coupled receptor family C group 6 member A (GPRC6A) and Dual oxidase 1 (Duox1) mediate a non-classical testosterone signaling pathway. However, the molecular mechanism in which testosterone mediates the GPRC6A-Duox1 cascade in the hair cycle was unclear. Therefore, this study aimed to elucidate the molecular role of the testosterone-GPRC6A-Duox1 signaling axis in regulating hair cycle progression and testosterone-mediated hair loss.</p><p><strong>Methods: </strong>GPRC6A-deficient and Duox1-deficient keratinocytes were prepared and stimulated with testosterone to assess hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) generation. Apoptosis was evaluated in primary keratinocytes from GPRC6A knockout (KO), Duox1 KO, and wild-type (WT) mice. Hair growth cycle progression was examined by measuring anagen phase duration and hair length. Ki-67 expression was analyzed as a marker of the anagen phase. To validate the testosterone-GPRC6A-Duox1 signaling network in androgenetic alopecia, testosterone was topically applied for one week to the back skin of WT, Duox1 KO, and GPRC6A KO mice on postnatal day 31 (P31).</p><p><strong>Results: </strong>GPRC6A-deficient and Duox1-deficient keratinocytes failed to induce H<sub>2</sub>O<sub>2</sub> generation in response to testosterone. Testosterone-dependent apoptosis in primary keratinocytes from GPRC6A KO and Duox1 KO mice was suppressed compared to keratinocytes from WT. The anagen phase of the hair growth cycle and hair lengths in GPRC6A KO and Duox1 KO mice were longer than WT consistent with the GPRC6A-Duox1 axis stimulating the anagen-to-catagen transition. The expression of Ki-67, a hallmark of the anagen phase, in GPRC6A KO and Duox1 KO mice was higher than that in WT. Duox1 KO and GPRC6A KO mice were resistant to testosterone-mediated hair loss, unlike WT.</p><p><strong>Conclusion: </strong>Taken together, these results suggest that the GPRC6A-Duox1 axis regulates natural hair cycles and testosterone-mediated hair loss.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"713-730"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781885","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":"Optimal Protocol for Differentiation of Human Tonsil-Derived Mesenchymal Stem Cells into Pancreatic β-like Cells.","authors":"Jiin Yang, Ha Yeong Kim, So Jeong Kim, Han Su Kim","doi":"10.1007/s13770-026-00806-4","DOIUrl":"10.1007/s13770-026-00806-4","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus, characterized by β-cell dysfunction and loss, results in impaired insulin secretion and chronic metabolic complications. Mesenchymal stem cells represent a promising source for β-cell regeneration owing to their endodermal differentiation potential. This study optimized the differentiation of human tonsil-derived mesenchymal stem cells (TMSCs) into pancreatic β-like cells through the comparative evaluation of two signaling-based protocols.</p><p><strong>Methods: </strong>TMSCs were isolated from human tonsils, and passages 5-7 were used for characterization and β-like cell differentiation. Two protocols were tested in both two-dimensional (2D) and three-dimensional (3D) cultures: Protocol I induced direct differentiation into pancreatic β-like cells without sequential developmental stages, whereas Protocol II followed stepwise progression from definitive endoderm to pancreatic progenitors, and finally pancreatic β-like cells.</p><p><strong>Results: </strong>In 2D culture, cells cultured under protocol II maintained a typical morphology and high confluency, whereas cells cultured under protocol I displayed a thinner shape with reduced confluency. Protocol II effectively induced definitive endoderm differentiation, as demonstrated by the increased expression of SOX17, FOXA2, and CXCR4 at the mRNA and protein levels. Both protocols upregulated pancreatic progenitor (HNF6 and NGN3) and pancreatic β-cell markers (Insulin, NKX6.1, and PDX1), but protocol II consistently produced higher pancreatic β-cell marker expression, except for MafA. In 3D spheroid culture, insulin, PDX1, and MafA levels increased, with protocol II showing superior expression over protocol I. Additionally, differentiated cells exhibited glucose-responsive C-peptide secretion, indicating the acquisition of early β-cell-like functional properties.</p><p><strong>Conclusion: </strong>Stepwise, developmentally guided differentiation (Protocol II) more effectively directs TMSCs toward pancreatic β cell lineage commitment, highlighting the importance of stage specific signaling cues and supporting the potential of TMSCs for pancreatic β cell-based regenerative applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"699-712"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781946","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}
Shuaishuai Zhang, Yanzheng Liu, Yue Zhu, Junrong Li, Songbai Zhang, Qian Zhang, Min Zhang, Hui Wang, Yanli Liu
{"title":"Pressure-Regulated Chondrogenesis of BMSCs: Static Negative Pressure Primes Differentiation through Apoptotic Vesicles.","authors":"Shuaishuai Zhang, Yanzheng Liu, Yue Zhu, Junrong Li, Songbai Zhang, Qian Zhang, Min Zhang, Hui Wang, Yanli Liu","doi":"10.1007/s13770-026-00812-6","DOIUrl":"10.1007/s13770-026-00812-6","url":null,"abstract":"<p><strong>Background: </strong>It was found that pressure can promote the regeneration and repair of cartilage defects based on bone marrow mesenchymal stem cells (BMSCs). Since the compressive microenvironment of the cartilage in vivo may change with different movement, the mechanobiological effects of different compressive condition on BMSCs, especially the impact for its chondrogenic differentiation and influence on the cartilage microenvironment, is what we concerned about.</p><p><strong>Methods: </strong>Rat BMSCs were cultured and subjected to various types of pressure stimulation for 1 h. The Cell Counting Kit-8 (CCK-8) assay was used to analyze cell proliferation, flow cytometry was employed to assess the cell cycle and apoptosis, confocal microscopy was used to observe the cytoskeleton, and transmission electron microscopy was performed to examine the cellular ultrastructure. RT-PCR was used to identify chondrogenic differentiation markers. Apoptotic vesicles derived from BMSCs were isolated by ultracentrifugation, and differentially expressed microRNAs in these vesicles under - 40 kPa compression were identified by transcriptome sequencing.</p><p><strong>Results: </strong>Specific pressure conditions promoted the proliferation of BMSCs, with dynamic pressure showing a stronger proliferative effect than static pressure. Higher static negative pressure (- 40 kPa) significantly increased the spreading area of BMSCs. Dynamic pressure is stronger than static pressure in promoting cytoskeletal rearrangement, stress fiber formation, and cartilage marker expression in BMSCs. Flow cytometry and transmission electron microscopy results show that both - 40 kPa static and 90 kPa dynamic pressures promote BMSCs apoptosis to some extent. Under - 40 kPa static negative pressure, the differentially expressed microRNAs in BMSCs-derived apoptotic vesicles are involved in stem cell maintenance and chondrogenic proliferation processes.</p><p><strong>Conclusion: </strong>Static negative pressure (- 40 kPa) induces apoptosis in bone marrow mesenchymal stem cells (BMSCs). Notably, compared to chemical induction with staurosporine (STS), BMSCs subjected to - 40 kPa mechanical stimulation display distinct microRNA expression profiles within apoptotic vesicles, specifically enriched in microRNAs implicated in stem cell fate determination and cartilage regeneration. These findings offer valuable insights into biomechanical strategies for optimizing tissue-engineered cartilage repair.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"731-751"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212309","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":"Effect of hUCMSC-sEV-Loaded GelMA Microspheres on Pulp/Dentin Repair and Regeneration.","authors":"Xinping Lu, Huidan Deng, Ruotong Mai, Jingyi Kang, Quanjie Li, Huijia Li, Tingting Liang, Qiuxue Chen, Yu Wu","doi":"10.1007/s13770-026-00809-1","DOIUrl":"10.1007/s13770-026-00809-1","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated the biocompatibility of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSC) loaded in gelatin methacryloyl hydrogel microspheres (sEVs@GM-MS), and examined their effects on the proliferation and migration of human dental pulp stem cells (hDPSCs)/human umbilical vein endothelial cells (HUVECs), as well as their capacity to promote endothelial cell tube formation. Pulpotomy in a rat molar model was used to assess sEVs@GM-MS as a potential pulp-capping agent.</p><p><strong>Methods: </strong>sEVs@GM-MS were prepared and physicochemically characterized. In vitro assessments included live/dead staining, Cell Counting Kit-8 (CCK-8), migration assay and tube formation assay. In vivo, 7 and 14 days after pulpotomized with sEVs@GM-MS, GM-MS, iroot BP or without any pulp capping material, rat molars were evaluated using hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining.</p><p><strong>Results: </strong>GM-MS exhibited a porous surface via scanning electron microscopy. PKH67-labeled sEVs@GM-MS showed sustained release of sEVs. The cell proliferation, migration, tube formation in the sEVs@GM-MS group were significantly enhanced compared with those of the NC and GM-MS groups (p < 0.05). In rat pulpotomy model, sEVs@GM-MS group exhibited significant cell proliferation, angiogenesis, and reparative dentinogenesis with immunocytochemical localization of PCNA, CD31 and DMP-1 compared to NC and GM-MS groups (p < 0.05). Compared with the BP group, the sEVs@GM-MS group showed no significant difference in DMP-1 positive expression (p > 0.05).</p><p><strong>Conclusion: </strong>sEVs@GM-MS demonstrated excellent biocompatibility, sustained hUCMSC-sEV release, and enhanced pulp/dentin repair and regenaration, highlighting their potential as a pulp-capping agent.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"753-770"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821056","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":"Impact of Probiotic-Adjunctive Vonoprazan-Amoxicillin Dual Therapy on Gut Microbiota and Clinical Symptoms in Helicobacter pylori Eradication.","authors":"YingYing Yang, ChunHui Lan, Zheng Jiang","doi":"10.1007/s13770-026-00803-7","DOIUrl":"10.1007/s13770-026-00803-7","url":null,"abstract":"<p><strong>Background: </strong>This study evaluates the impact of Bacillus subtilis dual-strain enteric-coated capsules combined with vonoprazan-amoxicillin (VA) therapy on Helicobacter pylori (Hp) eradication rates, gastrointestinal symptoms, adverse events (AEs), and gut microbiota.</p><p><strong>Methods: </strong>60 Hp-positive adults were enrolled, allocated to probiotic (n = 30) or placebo (n = 30) groups. Both groups received a 14-day VA dual therapy, with the probiotic group additionally receiving a 28-day Bacillus subtilis dual-strain capsule regimen and the placebo group receiving matched placebos. Outcomes included Hp eradication rates (intention-to-treat [ITT]/per-protocol [PP] analyses), Gastrointestinal Symptom Rating Scale (GSRS) scores, AEs, antibiotic susceptibility, and gut microbiota changes (16S rRNA sequencing).</p><p><strong>Results: </strong>ITT analysis showed identical eradication rates (93.33%) in both groups; PP analysis revealed 96.67% (probiotic) versus 93.33% (placebo). The probiotic group exhibited significantly lower GSRS scores at weeks 4 (T2) and 8 (T3), particularly for diarrhea and acid reflux, with milder AEs (severity score: 5). Probiotic supplementation reduced Hp resistance to metronidazole (26.67% vs. 60.00%) without affecting other antibiotics. Microbiota analysis demonstrated post-eradication reductions in gastric pathogens (e.g., Helicobacter) and increased beneficial bacteria (e.g., Lactobacillus). The probiotic group showed faster restoration of gut α-diversity (higher at T2), enriched butyrate producers (e.g., Blautia, Anaerobutyricum), and decreased opportunistic pathogens (e.g., Klebsiella).</p><p><strong>Conclusions: </strong>Although Bacillus subtilis supplementation did not enhance Hp eradication rates, it significantly improved gastrointestinal symptoms, reduced AEs, increased Hp susceptibility to metronidazole, and accelerated microbiota recovery, supporting its role in microbiome modulation during Hp eradication therapy.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"653-666"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781929","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}
Hye June Byun, Mi Yeon Ha, Gun-Jae Jeong, Dae Hyeok Yang, Jeong Ho Chang, Ju Woong Jang, Yasuhiko Iwasaki, Jae Taek Hong, Heung Jae Chun
{"title":"Poly(2-Methacryloxyethyl Phosphorylcholine-Co-Butyl Methacrylate) Coating Enhances Biomimetic Mineralization of Bioglass and Promotes Cellular Proliferation.","authors":"Hye June Byun, Mi Yeon Ha, Gun-Jae Jeong, Dae Hyeok Yang, Jeong Ho Chang, Ju Woong Jang, Yasuhiko Iwasaki, Jae Taek Hong, Heung Jae Chun","doi":"10.1007/s13770-026-00797-2","DOIUrl":"10.1007/s13770-026-00797-2","url":null,"abstract":"<p><strong>Background: </strong>Biologically active glasses (BG) are widely studied as potential materials for bone tissue engineering, owing to their capacity to form hydroxyapatite (HA) layers when exposed to body fluids. However, the demerit of BG is the slow deposition rate of calcium ions on the surface, a key factor in increasing the conversion rate to mineralization. The purpose of this study is to introduce phosphoryl group recognized as a trigger for the nucleation processes of apatite formation on the surface of BG.</p><p><strong>Methods: </strong>BG was coated with poly (2-methacryloyloxyethyl phosphorylcholine) (PMB) and characterized via Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Biomimetic mineralization was evaluated through simulated body fluid (SBF) immersion, X-ray diffraction (XRD). In vitro MG-63 cell responses were assessed and compared among BG, BG/HA, BG/2%PMB, and BG/2%PMB/HA groups.</p><p><strong>Results: </strong>Results demonstrated that the PMB coating successfully promoted mineralization by introducing negatively charged phosphate groups that enhanced crystallization. BG/2%PMB/HA significantly upregulated focal adhesion markers in MG-63 cells, likely due to improved fibronectin (Fn) deposition on the HA layer. Furthermore, the BG/2%PMB/HA surface enhanced cell survival and proliferation through crosstalk with integrin-mediated signaling pathways.</p><p><strong>Conclusions: </strong>PMB-coated BG effectively accelerates biomimetic mineralization and regulates cellular responses, making it a promising candidate for bone regeneration applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"639-651"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522033","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}
Yeeun Kim, Hee-Woong Yun, Sujin Noh, Sumin Lim, Jun Young Chung, Jae-Young Park, Do Young Park
{"title":"Optimizing Cell Isolation for Adipose- and Synovium Derived Mesenchymal Stem Cells from Infrapatellar Fat Pad.","authors":"Yeeun Kim, Hee-Woong Yun, Sujin Noh, Sumin Lim, Jun Young Chung, Jae-Young Park, Do Young Park","doi":"10.1007/s13770-026-00805-5","DOIUrl":"10.1007/s13770-026-00805-5","url":null,"abstract":"<p><strong>Background: </strong>The infrapatellar fat pad (IFP) is a rich source of mesenchymal stem cells (MSCs) with dual contributions from adipose and synovial tissues. The heterogeneity of IFP-derived MSCs and the lack of standardized isolation protocols, however, hinder consistent therapeutic outcomes. This study aimed to optimize collagenase-based isolation protocols for IFP-MSCs, with a focus on the effects of enzyme concentration and treatment duration on tissue digestion, cell origin, viability, and functional properties.</p><p><strong>Methods: </strong>IFP tissues harvested from patients undergoing knee arthroscopy were enzymatically digested using various collagenase concentrations (0.1-2%) and incubation times (2-48 h). Histological, immunohistochemical, flow cytometric, and functional assays were performed to evaluate tissue degradation, surface marker expression, colony-forming ability, and trilineage differentiation.</p><p><strong>Results: </strong>Milder digestion conditions (2 h, 0.2-0.4% collagenase) preferentially extracted synovial membrane MSCs (CD55<sup>+</sup> cells) and supported higher CFUs and chondrogenic/osteogenic differentiation. In contrast, prolonged digestion (48 h) led to increased cell yields and adipogenic differentiation, but reduced cell viability and percentage of synovial marker expression.</p><p><strong>Conclusion: </strong>In conclusion, enzymatic digestion parameters critically influence the cellular composition and regenerative potential of IFP-MSCs. Optimizing collagenase treatment conditions allows for a more selective, lineage-based MSC harvest, offering a practical strategy for tailored regenerative utilization of IFP-MSCs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"681-697"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646402","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}