Regenerative Therapy最新文献

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Lubricin maintains temporomandibular joint homeostasis by regulating synovial inflammation 润滑素通过调节滑膜炎症维持颞下颌关节稳态
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2025-12-04 DOI: 10.1016/j.reth.2025.101051
Soichiro Negishi , Kazuhiro Shibusaka , Miki Maemura , Masayuki Tsukasaki , Seigo Ohba , Sakae Tanaka , Taku Saito , Yutaka Suzuki , Hiroyuki Okada , Fumiko Yano
{"title":"Lubricin maintains temporomandibular joint homeostasis by regulating synovial inflammation","authors":"Soichiro Negishi ,&nbsp;Kazuhiro Shibusaka ,&nbsp;Miki Maemura ,&nbsp;Masayuki Tsukasaki ,&nbsp;Seigo Ohba ,&nbsp;Sakae Tanaka ,&nbsp;Taku Saito ,&nbsp;Yutaka Suzuki ,&nbsp;Hiroyuki Okada ,&nbsp;Fumiko Yano","doi":"10.1016/j.reth.2025.101051","DOIUrl":"10.1016/j.reth.2025.101051","url":null,"abstract":"<div><h3>Introduction</h3><div>Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative joint disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling, yet its molecular pathogenesis remains poorly understood. In this study, we investigated the role of proteoglycan 4 (<em>Prg4</em>), also known as lubricin, in maintaining temporomandibular joint (TMJ) homeostasis under physiological and pathological conditions, with the aim of exploring its potential for regenerative therapeutic applications.</div></div><div><h3>Methods</h3><div>Using high-resolution Visium HD spatial transcriptomics, we examined the spatial distribution of <em>Prg4</em> expression within the TMJ. To model TMJ-OA, surgically induced anterior disc displacement (ADD) was performed in wild-type (WT) and <em>Prg4</em>-knockout (Prg4-KO) mice. In addition, inflammatory stimulation with IL-1β was applied to synovial cells <em>in vitro</em>. Lineage tracing approaches were used to track <em>Prg4</em>-expressing cells under pathological conditions.</div></div><div><h3>Results</h3><div>Spatial transcriptomics revealed that <em>Prg4</em> expression was highly localized to the posterior synovium of the articular disc, with markedly lower expression in anterior regions. While sham-operated TMJs remained histologically intact, the ADD model resulted in condylar deformation, cartilage degeneration, synovial hyperplasia, and subchondral bone loss—phenotypes that were significantly exacerbated in Prg4-KO mice. Furthermore, IL-1β stimulation increased matrix metalloproteinase expression in <em>Prg4</em>-deficient synovial cells. Lineage tracing demonstrated expansion of <em>Prg4</em>-expressing cells within inflamed synovial tissues in the ADD model. Quantitative analysis revealed that <em>Prg4</em> expression was transiently increased at 2 weeks after ADD induction and returned to control levels by 8 weeks, indicating a time-dependent regulatory role during inflammation.</div></div><div><h3>Conclusion</h3><div>These findings highlight the region-specific and time-dependent function of <em>Prg4</em> in the TMJ and underscore its critical role in suppressing joint inflammation and degeneration. Importantly, our results suggest that modulation of <em>Prg4</em> expression or lubricin supplementation could serve as a regenerative therapeutic strategy for preserving TMJ homeostasis and preventing chronic degenerative progression, providing a promising avenue for clinical translation in TMJ-OA treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101051"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RAD51 promotes osteogenic differentiation and inhibits DNA damage in osteoporosis though regulating cGAS-STING signaling pathway RAD51通过调节cGAS-STING信号通路促进骨质疏松症成骨分化,抑制骨质疏松症DNA损伤
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2026-01-30 DOI: 10.1016/j.reth.2026.101070
Minli Qiu , Peili He , Zena Chen, Liuzhong Zhou, Xinyu Wu, Mingcan Yang, Yutong Jiang, Jieruo Gu
{"title":"RAD51 promotes osteogenic differentiation and inhibits DNA damage in osteoporosis though regulating cGAS-STING signaling pathway","authors":"Minli Qiu ,&nbsp;Peili He ,&nbsp;Zena Chen,&nbsp;Liuzhong Zhou,&nbsp;Xinyu Wu,&nbsp;Mingcan Yang,&nbsp;Yutong Jiang,&nbsp;Jieruo Gu","doi":"10.1016/j.reth.2026.101070","DOIUrl":"10.1016/j.reth.2026.101070","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis (OP) represents a metabolic bone disorder characterized by reduced bone density and increased fracture susceptibility, primarily caused by an imbalance between bone resorption and formation. Osteogenic differentiation plays a critical role in OP, as it promotes bone formation processes. RAD51, a crucial gene encoding a protein essential for homologous recombination repair of DNA double-strand breaks, is central to maintaining genomic stability and ensuring accurate DNA repair. Previous investigations conducted by our research team have suggested the involvement of RAD51 in the pathogenesis of OP. The objective of this study was to explore the signaling pathways associated with RAD51.</div></div><div><h3>Methods</h3><div>MC3T3-E1 cells were induced to undergo osteogenic differentiation and exposed to a microgravity environment to simulate OP-like conditions. Furthermore, an ovariectomized (OVX) mouse model was established to mimic OP. Osteogenic differentiation was evaluated through Alizarin Red S staining for calcium deposition and alkaline phosphatase (ALP) staining to assess ALP activity. DNA damage was quantified using the comet assay, while protein expression profiles were analyzed via Western blot.</div></div><div><h3>Results</h3><div>Experimental results showed a significant downregulation of RAD51 expression in OP models. Notably, RAD51 overexpression promoted osteoblast differentiation and mitigated DNA damage in these models. Mechanistic studies further revealed that RAD51 suppresses activation of the cGAS-STING signaling pathway, which has been shown to negatively regulate osteoblast differentiation. In OVX mice, RAD51 overexpression mitigated bone loss, promoted osteoblast differentiation, and reduced DNA damage.</div></div><div><h3>Conclusion</h3><div>RAD51 facilitated osteogenic differentiation and attenuated DNA damage in OP by modulating the cGAS-STING signaling pathway, offering a potential novel therapeutic target for OP treatment.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101070"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping the evolving landscape of conductive hydrogels in medicine: A bibliometric perspective 绘制导电水凝胶在医学中的发展图景:文献计量学视角
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2025-11-26 DOI: 10.1016/j.reth.2025.11.003
Jia Zhang , Yali Yang , Shuilan Bao , Yiren Wang , Zhongjian Wen , Shouying Chen , Li Yao , Ping Zhou , Yun Zhou , Ying Chen
{"title":"Mapping the evolving landscape of conductive hydrogels in medicine: A bibliometric perspective","authors":"Jia Zhang ,&nbsp;Yali Yang ,&nbsp;Shuilan Bao ,&nbsp;Yiren Wang ,&nbsp;Zhongjian Wen ,&nbsp;Shouying Chen ,&nbsp;Li Yao ,&nbsp;Ping Zhou ,&nbsp;Yun Zhou ,&nbsp;Ying Chen","doi":"10.1016/j.reth.2025.11.003","DOIUrl":"10.1016/j.reth.2025.11.003","url":null,"abstract":"<div><h3>Purpose</h3><div>This bibliometric study, based on 1,030 publications from the Web of Science Core Collection through December 31, 2024, explores the evolving landscape of conductive hydrogels in medicine.</div></div><div><h3>Methods</h3><div>This study uses tools like Bibliometrix, VOSviewer, and CiteSpace to investigate the research hotspots, collaborative patterns, and developmental trends of conductive hydrogels in the medical field from 2015 to 2024, thereby offering novel insights for future research in this domain.</div></div><div><h3>Results</h3><div>The analysis reveals a significant 38.04 % annual growth rate in publications since 2015. China leads in research output with 734 articles, followed by Korea. Key institutions, including Chinese Academy of Sciences, Sichuan University, and Xi'an Jiaotong University, have been instrumental in driving this field forward. Research hotspots, centered on high-performance scaffolds, are expanding into two main areas: synergistic tissue regeneration and drug delivery, and flexible, wearable point-of-care diagnostics. A key trend is the shift in focus from the hydrogel's material and structure (support, conductivity) to its performance and function (integrated mechanics, sensing, and wearability). This highlights the multidisciplinary potential of conductive hydrogels. Despite China's high publication volume, the study emphasizes that it requires deeper fundamental research and stronger international collaborations.</div></div><div><h3>Conclusions</h3><div>Future initiatives must emphasize the advancement of multifunctional hydrogel platforms, cultivate interdisciplinary collaborations integrating materials science, medicine, and engineering, and implement consistent preclinical assessment and regulatory frameworks. These strategic steps are crucial for moving hydrogel innovations from the lab to clinical applications, such as chronic wound healing, myocardial repair, and wearable diagnostics.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101038"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Qianzheng powder promotes facial nerve regeneration via BDNF/TrkB/CREB pathway activation 千正散通过激活BDNF/TrkB/CREB通路促进面神经再生
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2025-12-02 DOI: 10.1016/j.reth.2025.101048
Liang Chen, Chaoqun Wang, Lixin Jiang, Qiang Xie, Hongru Qin, Ziheng Zhang
{"title":"Qianzheng powder promotes facial nerve regeneration via BDNF/TrkB/CREB pathway activation","authors":"Liang Chen,&nbsp;Chaoqun Wang,&nbsp;Lixin Jiang,&nbsp;Qiang Xie,&nbsp;Hongru Qin,&nbsp;Ziheng Zhang","doi":"10.1016/j.reth.2025.101048","DOIUrl":"10.1016/j.reth.2025.101048","url":null,"abstract":"<div><h3>Introduction</h3><div>Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms.</div></div><div><h3>Methods</h3><div>A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&amp;E staining and serum biochemical markers.</div></div><div><h3>Results</h3><div>QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and <em>p</em>-CREB/CREB expressions in QZP-treated mice. No hepatic or renal toxicity was detected.</div></div><div><h3>Conclusion</h3><div>QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101048"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The favorable role of recombinant collagen peptide in periosteal cell-derived osteoregeneration 重组胶原肽在骨膜细胞源性骨再生中的有利作用
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.reth.2026.101064
Tran Thi Thuy Diep , Naoki Takahashi , Takahiro Tsuzuno , Shunya Motosugi , Yuta Ueda , Aoi Yamada , Yukari Aoki-Nonaka , Masaki Nagata , Koichi Tabeta
{"title":"The favorable role of recombinant collagen peptide in periosteal cell-derived osteoregeneration","authors":"Tran Thi Thuy Diep ,&nbsp;Naoki Takahashi ,&nbsp;Takahiro Tsuzuno ,&nbsp;Shunya Motosugi ,&nbsp;Yuta Ueda ,&nbsp;Aoi Yamada ,&nbsp;Yukari Aoki-Nonaka ,&nbsp;Masaki Nagata ,&nbsp;Koichi Tabeta","doi":"10.1016/j.reth.2026.101064","DOIUrl":"10.1016/j.reth.2026.101064","url":null,"abstract":"<div><h3>Background</h3><div>Human periosteal cells (hPCs) possess high osteogenic potential and are considered promising candidates for regenerative therapy. Recombinant human collagen peptide (RCP), a xeno-free biomaterial enriched with arginine-glycine-aspartic acid (RGD) sequences, provides a stable and biocompatible scaffold that may enhance cellular functions.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the biocompatibility of RCP with hPCs and its effects on osteogenic functions <em>in vitro</em> and in <em>vivo</em>.</div></div><div><h3>Materials and methods</h3><div>Cell viability was assessed by MTT assay at various RCP concentrations. Cell adhesion and migration were examined using fluorescence-based adhesion and Oris™ migration assays. Gene expression profiles were analyzed by RNA-sequencing and quantitative PCR. Alkaline phosphatase assay (ALP) and Alizarin Red staining (ARS) were performed to evaluate osteogenic differentiation. For <em>in vivo</em> analysis, a rat calvarial critical-size defect model was used to evaluate bone regeneration following transplantation of hPCs with or without RCP.</div></div><div><h3>Results</h3><div>RCP exhibited no cytotoxic effects and enhanced the adhesion and migration of hPCs. RNA-seq and qPCR analyses revealed upregulation of extracellular matrix- and osteogenesis-related genes, including COL1A1, SERPINH1, ALP, RUNX2, and OCN. Moreover, RCP enhanced osteogenic differentiation, as demonstrated by increased ALP activity and greater calcium deposition in ARS. <em>In vivo</em>, micro-CT analysis showed no significant difference in new bone volume among groups, whereas immunohistochemical analysis revealed increased numbers of OCN- and BMP-2-positive cells in RCP-treated defects, indicating enhanced osteogenic activity.</div></div><div><h3>Conclusion</h3><div>RCP supports the osteogenic potential of hPCs by promoting adhesion, migration, and osteogenesis-related gene expression, and enhancing osteogenic activity <em>in vitro</em> and <em>in vivo</em>. These findings suggest that RCP is a promising biomaterial for periosteal cell-based regenerative therapies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101064"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vitro polarized macrophages ameliorate adverse cardiac remodeling in a mouse model of transverse aortic constriction 在体外极化巨噬细胞改善不良心脏重塑在小鼠横断主动脉收缩模型
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.reth.2026.101061
Ulugbek Yakhshimurodov , Kizuku Yamashita , Takuji Kawamura , Kenji Miki , Takura Taguchi , Shunsuke Saito , Imad Abugessaisa , Shigeru Miyagawa
{"title":"In vitro polarized macrophages ameliorate adverse cardiac remodeling in a mouse model of transverse aortic constriction","authors":"Ulugbek Yakhshimurodov ,&nbsp;Kizuku Yamashita ,&nbsp;Takuji Kawamura ,&nbsp;Kenji Miki ,&nbsp;Takura Taguchi ,&nbsp;Shunsuke Saito ,&nbsp;Imad Abugessaisa ,&nbsp;Shigeru Miyagawa","doi":"10.1016/j.reth.2026.101061","DOIUrl":"10.1016/j.reth.2026.101061","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Heart failure (HF) caused by pressure overload remains as one of the leading causes of morbidity and mortality worldwide, which can manifest itself in a wide range of clinical scenarios. Current therapeutic strategies are limited to lifestyle changes, pharmacological measures, and devices aimed at supporting heart function. This poses a challenge in the search for new strategies for disease management. Macrophages, constituting nearly 10 % of non-myocyte cells in a healthy heart are considered a means to fill this gap due to their pleiotropic phenotype, which extends beyond the well-known functions of phagocytosis and antigen presentation. In this study, we evaluated the efficacy of bone marrow mononuclear cell (BMNC)-derived macrophages (BMNC-Mφ) in treating a mouse model of transverse aortic constriction (TAC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In &lt;em&gt;in vitro&lt;/em&gt; experiments, BMNC were polarized into BMNC-Mφ using a previously established protocol. We then performed transcriptomic analysis to confirm BMNC-Mφ marker genes compared to BMNC. BMNC-Mφ phenotypes were further validated by flow cytometry and RT-qPCR. In &lt;em&gt;in vivo&lt;/em&gt; experiments, all mice underwent TAC surgery (day 0). On days 7 and 14 post-TAC, mice in the experimental and control groups received intravenous injections of approximately 3 × 10&lt;sup&gt;6&lt;/sup&gt; BMNC-Mφ or PBS, respectively. Heart function was assessed weekly by transthoracic echocardiography at baseline and 7, 14, 21, and 28 days post-TAC. Additionally, we monitored &lt;em&gt;in vivo&lt;/em&gt; transcriptome dynamics over time using time-resolved deep RNA sequencing profiles of heart tissues from healthy, 1 day post-TAC, 8 days post-TAC, and 16 days post-TAC mice. Time-course transcriptomic profiling was followed by histological analysis of excised hearts on day 28.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;BMNC-Mφ showed phenotype similar to that of resident cardiac macrophages, with increased expression of key anti-inflammatory macrophage markers, including &lt;em&gt;Igf1, Arg1, Retnla, Ang2, Anxa2,&lt;/em&gt; and others. &lt;em&gt;In vivo&lt;/em&gt; application of BMNC-Mφ further confirmed their potential to mitigate adverse cardiac remodeling in TAC model. Mice receiving BMNC-Mφ better tolerated mechanical stress, as reflected in preserved LV function (LVEF [52.3 % vs. 45.6 %, p = 0.0152], LVFS [22.6 % vs. 19.2 %, p = 0.0208], and LVIDs [2.65 mm vs. 3.2 mm, p = 0.0261]), as well as structure (fibrosis area [5.6 % vs. 10.67 %, p &lt; 0.01]). In addition, BMNC-Mφ promoted angiogenesis (2120.4 ± 25.5 per mm&lt;sup&gt;2&lt;/sup&gt; vs. 1512.4 ± 34 per mm&lt;sup&gt;2&lt;/sup&gt;, p &lt; 0.05) and controlled cardiomyocyte growth, which was seen in the smaller short-axis diameter of cardiomyocytes in BMNC-Mφ-treated group (17.2 ± 0.18 μm vs. 19.45 ± 0.46 μm, p &lt; 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The main conclusion drawn from our results is that BMNC-Mφ improved or at least preserved LV function and architecture through metabolic recove","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101061"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Low-dose lipopolysaccharide pretreatment enhanced the proliferation and antibacterial activity of human adipose-derived mesenchymal stem cells 低剂量脂多糖预处理可增强人脂肪源性间充质干细胞的增殖和抗菌活性
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 10.1016/j.reth.2025.101057
Linling Li , Jielin Diao , Feng Wang , Xia Wang , Yicai Liu , Xiaoming Fu
{"title":"Low-dose lipopolysaccharide pretreatment enhanced the proliferation and antibacterial activity of human adipose-derived mesenchymal stem cells","authors":"Linling Li ,&nbsp;Jielin Diao ,&nbsp;Feng Wang ,&nbsp;Xia Wang ,&nbsp;Yicai Liu ,&nbsp;Xiaoming Fu","doi":"10.1016/j.reth.2025.101057","DOIUrl":"10.1016/j.reth.2025.101057","url":null,"abstract":"<div><h3>Introduction</h3><div>Adipose-derived mesenchymal stem cells (ADSCs) have been widely investigated for their pro-angiogenic and immunomodulatory roles in the repair of infected wounds. However, the direct antimicrobial effects of ADSCs and the underlying regulatory mechanisms remain poorly characterized. In particular, the functional modulation of ADSCs by low-dose lipopolysaccharide (LPS) preconditioning has not been systematically investigated.</div></div><div><h3>Methods</h3><div>We evaluated the effects of LPS preconditioning on the proliferation and apoptosis of human ADSCs (hADSCs), as well as the antimicrobial activity and wound-healing potential of hADSC-conditioned medium (hADSC-CM).</div></div><div><h3>Results</h3><div>Analysis demonstrated that at concentrations ranging from 10 to 500 ng/mL, LPS significantly enhanced the proliferation of hADSCs, with the highest viability observed at 500 ng/mL and no evidence of increased apoptosis. Moreover, LPS preconditioning markedly upregulated the expression of antimicrobial peptides (LL-37 and HBD-2) in hADSC-CM, leading to improved inhibition of <em>Staphylococcus aureus</em> and <em>Escherichia coli</em> growth. In vivo experiments further confirmed that 500 ng/mL of LPS-hADSC-CM significantly accelerated the healing of infected wounds, increased collagen deposition, and downregulated the expression of iNOS, thus suggesting enhanced inflammation resolution and tissue regeneration.</div></div><div><h3>Conclusion</h3><div>These findings highlight the capacity of LPS preconditioning to potentiate the biological functions of hADSCs, enhancing the antimicrobial and regenerative efficacy of hADSC-CM, and providing a promising strategy for the treatment of chronically infected wounds.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101057"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Smart integrated biomaterial systems for precision and optimized delivery of MSCs and their exosomes: Transforming wound healing and organ regeneration 用于MSCs及其外泌体精确和优化递送的智能集成生物材料系统:转化伤口愈合和器官再生
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2025-11-26 DOI: 10.1016/j.reth.2025.101045
Fatemeh Rafati , Zeynab Ghorbani , Tahereh Manoochehrabadi , Farbod Khosravi , Jila Majidi , Fatemeh Eskandari , Mohamad Eftekhary , Hajar Nasiri
{"title":"Smart integrated biomaterial systems for precision and optimized delivery of MSCs and their exosomes: Transforming wound healing and organ regeneration","authors":"Fatemeh Rafati ,&nbsp;Zeynab Ghorbani ,&nbsp;Tahereh Manoochehrabadi ,&nbsp;Farbod Khosravi ,&nbsp;Jila Majidi ,&nbsp;Fatemeh Eskandari ,&nbsp;Mohamad Eftekhary ,&nbsp;Hajar Nasiri","doi":"10.1016/j.reth.2025.101045","DOIUrl":"10.1016/j.reth.2025.101045","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) and their exosome (MSCs-Exos) have been shown to be major therapeutic candidates in regenerative medicine due to their inherent capacity for modulating immune response, promoting angiogenesis, and repairing tissues. However, clinical application of MSCs and MSCs-Exos is hindered by various intrinsic barriers, such as poor survival of transplanted MSCs, quick systemic clearance of exosomes, uncontrolled release of therapeutic payloads, and loss of function in severe pathological situations, such as chronic wounds and fibrotic tissues. To overcome these limitations, recent advances have focused on the design of modern delivery systems to enhance the stability, bioavailability, and functionality of MSCs and MSCs-Exos. These platforms include responsive hydrogels, engineered nanoparticles, and multi responsive intelligent dressings that mirror protective microenvironments in general and provide controlled, long-term distribution of bioactive elements. This current review focuses on such innovative approaches that enhance regeneration results in strong preclinical models, maximize therapeutic delivery, and boost MSCs and exosome survival. Despite remarkable advancements, major obstacles still exist, such as guaranteeing biosafety, achieving scale production, and obtaining regulatory approvals. The combination of MSCs and MSCs-Exos therapies with intelligent, responsive biomaterials capable of providing antimicrobial function and active monitoring has the potential to revolutionize tissue regeneration and wound healing and make MSCs and MSCs-Exos invaluable resources in precision regenerative medicine of the future.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101045"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Innovative synergy of bone xenograft and quercetin in the alveolar bone socket: Histological and immunohistochemical assessment of healing 牙槽骨窝中异种骨移植和槲皮素的创新协同作用:愈合的组织学和免疫组织化学评估
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2026-02-11 DOI: 10.1016/j.reth.2026.101076
Christian Khoswanto , Ira Kusuma Dewi
{"title":"Innovative synergy of bone xenograft and quercetin in the alveolar bone socket: Histological and immunohistochemical assessment of healing","authors":"Christian Khoswanto ,&nbsp;Ira Kusuma Dewi","doi":"10.1016/j.reth.2026.101076","DOIUrl":"10.1016/j.reth.2026.101076","url":null,"abstract":"<div><h3>Background</h3><div>After an extraction, the alveolar bone may undergo shrinkage, making it more challenging to place dental implants and compromising the appearance of prosthetic rehabilitation. Studies show that alveolar bone resorption could reach 50% of the original ridge width within the first six months after extraction. Xenografts have shown promising outcomes because they are biocompatible, resemble human bone, and facilitate the growth of new bone. Xenografts, on the other hand, are mostly used as a scaffold for new bone to grow on and don't cause bone growth on their own. Because of this, their integration and remodeling often take a long time and don't always happen completely. This has led researchers to look into other biological agents that can speed up healing and bone growth. Quercetin has been shown to be bioactive, meaning it can fight inflammation and act as an antioxidant. Using a bone xenograft or another suitable carrier or scaffold with quercetin may make it more stable and concentrated at the defect site. This combination may provide the osteoconductive framework necessary for new bone deposition, as well as the osteopromotive qualities of quercetin, to accelerate the cellular and molecular processes related to healing.</div></div><div><h3>Methods</h3><div>This study involved 64 healthy Wistar rats. The animals were randomly divided into four groups. The animals were euthanized seven to twenty-one days after extraction.</div><div>Combining quercetin with a xenogenic bone graft greatly speeds up the repair of the alveolar socket. The combination encourages the production of new bone early on.</div></div><div><h3>Conclusion</h3><div>The combination of quercetin and bone xenograft significantly improved the repair of alveolar bone sockets in Wistar rats.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101076"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146187795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microbial contamination risks and clinical safety in platelet-rich plasma therapy and evaluation of rapid microbial detection methods 富血小板血浆治疗中的微生物污染风险和临床安全性及快速微生物检测方法的评价
IF 3.5 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2026-03-01 Epub Date: 2025-11-17 DOI: 10.1016/j.reth.2025.11.008
Anna Arita , Yoshitomo Saita , Naho Fujiwara , Yasuhiro Homma , Morikuni Tobita
{"title":"Microbial contamination risks and clinical safety in platelet-rich plasma therapy and evaluation of rapid microbial detection methods","authors":"Anna Arita ,&nbsp;Yoshitomo Saita ,&nbsp;Naho Fujiwara ,&nbsp;Yasuhiro Homma ,&nbsp;Morikuni Tobita","doi":"10.1016/j.reth.2025.11.008","DOIUrl":"10.1016/j.reth.2025.11.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Platelet-rich plasma (PRP) is widely used for pain relief, wound healing, and so on. However, recent reports have documented cases of infections occurring after PRP therapy. In this study, we aimed to examine potential microbial contamination risks associated with PRP therapy and evaluate rapid microbial detection methods suitable for clinical use.</div></div><div><h3>Methods</h3><div>We assessed the risk of microbial contamination during blood collection, PRP preparation, and sterility testing. To evaluate suitable detection methods, we compared the microbial detection sensitivities of flow cytometry (FCM) and polymerase chain reaction (PCR) for identifying microbial contamination in PRP. For this purpose, PRP samples were inoculated with <em>Staphylococcus aureus</em>, <em>Streptococcus</em> spp., <em>Cutibacterium acnes</em>, <em>Micrococcus</em> spp., <em>Bacillus subtilis</em>, and <em>Candida albicans</em>.</div></div><div><h3>Results</h3><div>Following skin disinfection, microbial colonies were detected at the venipuncture site in six out of ten patients. Environmental monitoring identified airborne microbial colonies in two out of three anonymous PRP preparation facilities. Sterility tests revealed negative results for all 85 residual PRP and 15 platelet-poor plasma (PPP) cases. FCM sensitivity for microbial detection in PRP was effective at a concentration of 10<sup>2</sup>–10<sup>3</sup> colony forming units (cfu)/mL or higher. While <em>C. albicans</em> could not be detected separately from non-specific PRP signals using FCM, it was detectable in PPP at ≥10<sup>2</sup> cfu/mL. PCR sensitivity for microbial detection was excellent when analyzing pure microbial suspensions, however, it yielded a high rate of false-negative and false-positive results when PRP samples contained certain microbial strains.</div></div><div><h3>Conclusion</h3><div>The risks of microbial contamination were identified during both venipuncture and PRP production. To reduce these risks, it may be necessary to improve disinfection protocols for venipuncture sites and blood collection methods, implementing appropriate facility-specific measures. Although requiring further detection sensitivity improvements, FCM is a promising method for detecting viable bacteria in PRP. Given that microbial contamination cannot be completely eliminated, clinicians providing PRP therapy should remain alert to the potential for postoperative infections and ensure appropriate follow-up protocols are established.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"31 ","pages":"Article 101043"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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