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Objective evaluation of platelet-rich plasma mesotherapy on facial skin quality: An interim split-face analysis using an advanced imaging system 目的评价富血小板等离子体治疗对面部皮肤质量的影响:一项使用先进成像系统的中期面部分裂分析
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-23 DOI: 10.1016/j.reth.2025.10.008
Masashi Umeda, Takahiko Tamura, Kohki Okumura, Reiko Kiuchi, Hiroo Teranishi

Introduction

Autologous platelet-rich plasma (PRP), which is rich in growth factors, is widely used in aesthetic medicine to improve facial skin quality. However, its efficacy has been largely supported by subjective evaluations and case reports; objective and quantitative evidence remains limited. This study aimed to objectively and quantitatively evaluate the effects of PRP mesotherapy on facial skin quality, using a validated image analysis system.

Methods

Nine healthy adults (six females and three males; median age, 34 years) employed at the Tokyo Chuo Beauty Clinic were enrolled in this study. A split-face design was used, with PRP injected into the left hemiface and saline injected into the right hemiface under identical conditions (5 mL each). Facial images were obtained at baseline, two weeks, and one month using the NeoVoir system, which automatically identifies ten facial regions and extracts multiple quantitative skin parameters. The percentage change from baseline was compared between the sides.

Results

The primary endpoint, the gloss area at one month, showed a significantly greater increase on the PRP-treated side than on the saline-treated side (median difference, 16.3 %; p = 0.0039). At two weeks, the gloss also improved more on the PRP side, although the difference was not significant after false discovery rate (FDR) correction. Pore scores showed a greater reduction on the PRP side at one month (median difference, −17.6 %; p = 0.0039), but this result did not remain statistically significant after FDR adjustment (q = 0.0663). No significant differences were observed in wrinkle area, melanin content, or pigmentation indices. No serious adverse events occurred; only transient, mild local reactions such as redness and swelling were noted on both sides.

Conclusion

This study provides novel objective evidence that PRP mesotherapy significantly improves facial gloss, a key feature of healthy young skin. An exploratory trend toward pore reduction was also observed, although mechanistic interpretations remain hypothesized owing to the absence of biophysical and structural measurements. Moving beyond subjective assessments, these findings support the potential of PRP for enhancing facial brightness, smoothness, and overall skin quality. Further studies with larger cohorts, extended follow-ups, and multimodal evaluations are warranted to validate and expand upon these preliminary results.
自体富血小板血浆(PRP)富含生长因子,在美容医学中被广泛应用于改善面部皮肤质量。然而,其有效性在很大程度上得到了主观评价和病例报告的支持;客观和定量的证据仍然有限。本研究旨在使用一种经过验证的图像分析系统,客观定量地评估PRP化疗对面部皮肤质量的影响。方法在东京中央美容诊所工作的9名健康成年人(6名女性,3名男性,中位年龄34岁)加入本研究。采用裂面设计,在相同条件下左半边脸注射PRP,右半脸注射生理盐水(各5ml)。使用NeoVoir系统在基线、两周和一个月获得面部图像,该系统自动识别10个面部区域并提取多个定量皮肤参数。比较双方从基线的百分比变化。结果主要终点(1个月时的光泽面积)显示,prp治疗组比盐水治疗组明显增加(中位数差异为16.3%;p = 0.0039)。两周后,PRP方面的光泽度也得到了更多的改善,尽管在错误发现率(FDR)校正后差异并不显著。一个月后,PRP侧的孔隙评分下降幅度更大(中位数差值为- 17.6%;p = 0.0039),但在FDR调整后,这一结果没有统计学意义(q = 0.0663)。在皱纹面积、黑色素含量或色素沉着指数方面没有观察到显著差异。未发生严重不良事件;只有短暂的,轻微的局部反应,如两侧红肿。结论:本研究提供了新的客观证据,证明PRP疗法可显著改善面部光泽,这是健康年轻皮肤的关键特征。尽管由于缺乏生物物理和结构测量,机制解释仍然是假设的,但也观察到孔隙减少的探索性趋势。超越主观评估,这些发现支持PRP在提高面部亮度、平滑度和整体皮肤质量方面的潜力。进一步的研究需要更大的队列、更长的随访和多模式评估来验证和扩展这些初步结果。
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引用次数: 0
Sulfated hyaluronic acid for wound repair: Mechanisms, materials, and translational challenges 硫酸透明质酸用于伤口修复:机制、材料和转化挑战
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-18 DOI: 10.1016/j.reth.2025.10.006
Min Lin , Danni Zhou , Kaixuan Chen , Hankang Jiang , Wenjie Chen , Jing Wu , Guizhi Zhu , Kailei Xu , Peng Wei
Sulfated hyaluronic acid (sHA) is emerging as a promising biomaterial for advanced wound dressings because it combines the intrinsic biocompatibility and extracellular matrix (ECM)-like hydration of hyaluronic acid (HA) with added chemical functionality that enhances stability and bioactivity. Chronic wounds, particularly diabetic ulcer, —remain a major clinical challenge due to persistent inflammation, protease/reactive oxygen species (ROS)-rich microenvironments, impaired angiogenesis, and poor growth-factor retention; native HA is limited by rapid enzymatic degradation, low protein affinity, and potentially pro-inflammatory low-molecular fragments, motivating strategies to introduce sulfate groups onto HA to tune its interactions with cells and proteins. In this review, we performed a comprehensive literature review of the biological functions and applications of sHA in wound healing. Key results demonstrate that sHA significantly enhances anti-inflammatory responses, promotes sustained release of cationic therapeutics, improves angiogenesis, and reduces fibrosis. Furthermore, sHA-functionalized hydrogels accelerate diabetic wound healing by modulating macrophage polarization, enhancing re-epithelialization, and supporting vascularization. In further, we also offered a practical roadmap for researchers and clinicians to rationally design next-generation sHA-based dressings with improved reproducibility, controlled release, and safety.
硫酸透明质酸(sHA)是一种很有前途的生物材料,用于高级伤口敷料,因为它结合了透明质酸(HA)固有的生物相容性和细胞外基质(ECM)样水合作用,并增加了化学功能,增强了稳定性和生物活性。慢性伤口,特别是糖尿病性溃疡,由于持续的炎症、蛋白酶/活性氧(ROS)丰富的微环境、血管生成受损和生长因子保留不良,仍然是一个主要的临床挑战;天然透明质酸受酶促降解速度快、蛋白质亲和力低和潜在的促炎低分子片段的限制,促使将硫酸盐基团引入透明质酸以调节其与细胞和蛋白质的相互作用。在这篇综述中,我们对sHA的生物学功能和在伤口愈合中的应用进行了全面的文献综述。关键结果表明,sHA显著增强抗炎反应,促进阳离子疗法的持续释放,促进血管生成,减少纤维化。此外,sha功能化的水凝胶通过调节巨噬细胞极化、增强再上皮化和支持血管化来加速糖尿病伤口愈合。此外,我们还为研究人员和临床医生提供了一个实用的路线图,以合理设计下一代基于sha的敷料,提高可重复性,控释性和安全性。
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引用次数: 0
Sevoflurane suppresses LPS-induced microglia injury by regulating USP11-mediated UHRF1 deubiquitination 七氟醚通过调节usp11介导的UHRF1去泛素化抑制lps诱导的小胶质细胞损伤
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-17 DOI: 10.1016/j.reth.2025.09.004
Dongzhi Liu, Chengliang Sun, Xiuli Zhang, Shunheng Gao

Background

Spinal cord injury (SCI) is a devastating neurological and pathological condition that leads to severe motor, sensory, and autonomic dysfunctions. The neuroprotective effect of Sevoflurane (Sevo) in the rat model of SCI has been reported. However, the mechanism of Sevo is still elusive.

Methods

24 rats were divided into four groups: sham group, sham + Sevo group, SCI group, and SCI + Sevo group. On days 0, 14, 28, and 42 post-SCI, functional recovery was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE staining. Western blotting, ELISA, and corresponding kits were used to detect the effects of Sevo on apoptosis, inflammatory factors, and oxidative stress. Human microglia HMC3 were induced by lipopolysaccharide (LPS) to mimic the in vitro environment of SCI. Ubiquitin-specific peptidase 11 (USP11) and ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), B-cell lymphoma-2 (BCL-2), and Bcl-2 related X protein (BAX) protein levels were determined using Western blot. Cell apoptosis, Interleukin-1β (IL-1β), and IL-6 levels were assessed using flow cytometry and ELISA. malondialdehyde (MDA), glutathione (GSH), and Reactive oxygen species (ROS) products were examined using special assay kits. After Ubibrowser prediction, GO enrichment, and protein-protein interaction (PPI) networks, the interaction between USP11 and UHRF1 was verified using Co-immunoprecipitation (CoIP) assay.

Results

Sevo treatment improved spinal cord functional recovery in rats, as evidenced by enhanced BBB locomotor rating scale and neuron death in vivo. Meanwhile, Sevo also reduced inflammation and oxidative damage in rats following SCI. Sevo exposure decreased USP11 and UHRF1 expression in LPS-treated HMC3 cells. Sevo repressed LPS-triggered HMC3 cell apoptosis, inflammatory response, and oxidative stress promotion by regulating USP11. At the molecular level, USP11 interacted with UHRF1 and maintained its stabilization by removing ubiquitin.

Conclusion

Sevo could protect LPS-induced HMC3 cell apoptosis, inflammation, and oxidative stress by regulating the USP11/UHRF1 axis, which might provide a novel therapeutic mechanism for Sevo in SCI.
脊髓损伤(SCI)是一种毁灭性的神经和病理状况,可导致严重的运动、感觉和自主神经功能障碍。报道了七氟醚(Sevo)在脊髓损伤大鼠模型中的神经保护作用。然而,Sevo的机制仍然是难以捉摸的。方法将24只大鼠分为4组:sham组、sham + Sevo组、SCI组、SCI + Sevo组。在脊髓损伤后第0、14、28和42天,采用血脑屏障试验评估功能恢复情况。HE染色观察脊髓组织学改变。采用Western blotting、ELISA及相应试剂盒检测Sevo对细胞凋亡、炎症因子和氧化应激的影响。采用脂多糖(LPS)诱导人小胶质细胞HMC3模拟体外脊髓损伤环境。Western blot检测泛素特异性肽酶11 (USP11)和泛素样蛋白,含PHD和环指结构域1 (UHRF1)、b细胞淋巴瘤-2 (BCL-2)和BCL-2相关X蛋白(BAX)蛋白水平。采用流式细胞术和ELISA检测细胞凋亡、白细胞介素-1β (IL-1β)和IL-6水平。丙二醛(MDA)、谷胱甘肽(GSH)和活性氧(ROS)产物采用特殊检测试剂盒检测。在Ubibrowser预测、氧化石墨烯富集和蛋白蛋白相互作用(PPI)网络之后,USP11和UHRF1之间的相互作用通过共免疫沉淀(CoIP)试验得到验证。结果svo治疗可改善大鼠脊髓功能恢复,血脑屏障运动评分和神经元死亡均有明显提高。同时,Sevo还能减轻大鼠脊髓损伤后的炎症和氧化损伤。在lps处理的HMC3细胞中,连续暴露降低了USP11和UHRF1的表达。通过调节USP11, Sevo抑制lps引发的HMC3细胞凋亡、炎症反应和氧化应激促进。在分子水平上,USP11与UHRF1相互作用,并通过去除泛素维持其稳定性。结论Sevo通过调控USP11/UHRF1轴对lps诱导的HMC3细胞凋亡、炎症和氧化应激具有保护作用,这可能为Sevo治疗脊髓损伤提供了一种新的机制。
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引用次数: 0
Targeting ER stress-mediated apoptosis by MSC-derived exosomes: A novel therapeutic strategy against pulmonary fibrosis 骨髓间质干细胞衍生外泌体靶向内质网应激介导的细胞凋亡:一种治疗肺纤维化的新策略
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-17 DOI: 10.1016/j.reth.2025.10.004
Ruixi Luo, Yaqiong Wei, La Wang, Peng Chen, Didong Lou, Weiyi Tian

Introduction

Idiopathic pulmonary fibrosis (IPF) is marked by a gradual decline in pulmonary function over time and is associated with a grim prognosis. In the pathogenesis of IPF, persistent endoplasmic reticulum (ER) stress plays a significant role in promoting fibrosis through pathways involving apoptosis. Mesenchymal stem cell-derived exosomes (MSC-Ex) have shown promise in mitigating pulmonary fibrosis by inhibiting apoptosis. Nonetheless, the precise mechanisms underlying this effect remain unclear. In our previous findings, we demonstrated that MSCs alleviate pulmonary fibrosis by regulating ER stress. Building upon this, we sought to investigate whether MSC-Ex could mitigate alveolar epithelial cell apoptosis through the ER stress pathway. We posited that targeting ER stress could represent a crucial mechanism by which MSC-Ex alleviate apoptosis in IPF models.

Methods and results

In this study, bleomycin (BLM) induced apoptosis in A549 cells, and MSC-Ex treatment reduced apoptotic cells and the Bax/Bcl-2 ratio. ER stress is involved in BLM-induced apoptosis in A549 cells, and MSC-Ex reduced ER stress-related protein (Bip and CHOP) expression and reversed the morphological changes of the ER in A549 cells. Moreover, blockade of ER stress with ER stress inhibitor TUDCA contributed to the amelioration of apoptosis in A549 cells, indicating that MSC-Ex reduced BLM-induced apoptosis at least partly by modulating ER stress. In vivo, MSC-Ex injection decreased BLM-induced pulmonary fibrosis in mice, as well as ER stress and apoptosis in the lung tissues.

Conclusions

In conclusion, ER stress induced apoptosis in BLM-treated A549 cells, and MSC-Ex treatment mitigated apoptosis via inhibiting ER stress. This study provides a novel mechanism for MSC-Ex-mediated protection on apoptosis in an IPF model and suggests that MSC-Ex could be a promising therapeutic strategy for IPF.
特发性肺纤维化(IPF)的特点是随着时间的推移肺功能逐渐下降,预后不佳。在IPF的发病机制中,持续内质网(ER)应激通过涉及细胞凋亡的途径在促进纤维化中起重要作用。间充质干细胞来源的外泌体(MSC-Ex)已显示出通过抑制细胞凋亡来减轻肺纤维化的前景。尽管如此,这种效应背后的确切机制仍不清楚。在我们之前的研究中,我们证明了间充质干细胞通过调节内质网应激来减轻肺纤维化。在此基础上,我们试图研究MSC-Ex是否可以通过内质网应激途径减轻肺泡上皮细胞凋亡。我们假设靶向内质网应激可能是MSC-Ex减轻IPF模型中细胞凋亡的关键机制。方法和结果在本研究中,博来霉素(BLM)诱导A549细胞凋亡,MSC-Ex处理可降低凋亡细胞数和Bax/Bcl-2比值。内质网应激参与了blm诱导的A549细胞凋亡,MSC-Ex可降低内质网应激相关蛋白(Bip和CHOP)的表达,逆转A549细胞内质网形态学变化。此外,内质网应激抑制剂TUDCA阻断内质网应激有助于改善A549细胞的凋亡,这表明MSC-Ex至少在一定程度上通过调节内质网应激来减少blm诱导的细胞凋亡。在体内,MSC-Ex注射液可减轻blm诱导的小鼠肺纤维化,减少肺组织内质网应激和细胞凋亡。结论内质网应激可诱导blm处理的A549细胞凋亡,而MSC-Ex可通过抑制内质网应激减轻细胞凋亡。本研究提供了一种新的MSC-Ex在IPF模型中介导细胞凋亡保护的机制,并表明MSC-Ex可能是一种有前景的IPF治疗策略。
{"title":"Targeting ER stress-mediated apoptosis by MSC-derived exosomes: A novel therapeutic strategy against pulmonary fibrosis","authors":"Ruixi Luo,&nbsp;Yaqiong Wei,&nbsp;La Wang,&nbsp;Peng Chen,&nbsp;Didong Lou,&nbsp;Weiyi Tian","doi":"10.1016/j.reth.2025.10.004","DOIUrl":"10.1016/j.reth.2025.10.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Idiopathic pulmonary fibrosis (IPF) is marked by a gradual decline in pulmonary function over time and is associated with a grim prognosis. In the pathogenesis of IPF, persistent endoplasmic reticulum (ER) stress plays a significant role in promoting fibrosis through pathways involving apoptosis. Mesenchymal stem cell-derived exosomes (MSC-Ex) have shown promise in mitigating pulmonary fibrosis by inhibiting apoptosis. Nonetheless, the precise mechanisms underlying this effect remain unclear. In our previous findings, we demonstrated that MSCs alleviate pulmonary fibrosis by regulating ER stress. Building upon this, we sought to investigate whether MSC-Ex could mitigate alveolar epithelial cell apoptosis through the ER stress pathway. We posited that targeting ER stress could represent a crucial mechanism by which MSC-Ex alleviate apoptosis in IPF models.</div></div><div><h3>Methods and results</h3><div>In this study, bleomycin (BLM) induced apoptosis in A549 cells, and MSC-Ex treatment reduced apoptotic cells and the Bax/Bcl-2 ratio. ER stress is involved in BLM-induced apoptosis in A549 cells, and MSC-Ex reduced ER stress-related protein (Bip and CHOP) expression and reversed the morphological changes of the ER in A549 cells. Moreover, blockade of ER stress with ER stress inhibitor TUDCA contributed to the amelioration of apoptosis in A549 cells, indicating that MSC-Ex reduced BLM-induced apoptosis at least partly by modulating ER stress. <em>In vivo,</em> MSC-Ex injection decreased BLM-induced pulmonary fibrosis in mice, as well as ER stress and apoptosis in the lung tissues.</div></div><div><h3>Conclusions</h3><div>In conclusion, ER stress induced apoptosis in BLM-treated A549 cells, and MSC-Ex treatment mitigated apoptosis via inhibiting ER stress. This study provides a novel mechanism for MSC-Ex-mediated protection on apoptosis in an IPF model and suggests that MSC-Ex could be a promising therapeutic strategy for IPF.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 933-945"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319883","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
Multimodal mechanisms of platelet-rich plasma in bone defect repair: Angiogenesis, inflammation modulation, and metabolic regulation 富血小板血浆在骨缺损修复中的多模式机制:血管生成、炎症调节和代谢调节
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-15 DOI: 10.1016/j.reth.2025.09.007
Junjie Chen , Bo Liu , Jiayang He , Yuhao Wei , Yuhan He , Hang Zhou , Zhiqiang Zhang , Yiwen Weng , Ming Cheng
Bone defect is the loss of bone tissue due to trauma, fracture, infection, etc. This loss may lead to non-union of fracture, bone defect or bone deficiency, which seriously affects the patient's quality of life and even leads to dysfunction and disability. Although surgical repair is a common treatment modality, the surgical procedure is complicated, with a long postoperative recovery period and certain surgical risks, such as infection and bleeding. Platelet-rich plasma (PRP), as a novel therapeutic approach, has demonstrated remarkable potential in bone defect repair. PRP is rich in growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), etc., and can have a beneficial effect on bone defect repair through various mechanisms, such as the release of growth factors, the promotion of angiogenesis, the inhibition of inflammatory response, and the recruitment of activated cells and other mechanisms, which play a positive role in the repair of bone defects and provide strong support for the regeneration and repair of bone tissue.
骨缺损是指由于外伤、骨折、感染等导致的骨组织丢失。这种损失可能导致骨折不愈合、骨缺损或骨缺乏,严重影响患者的生活质量,甚至导致功能障碍和残疾。虽然手术修复是常见的治疗方式,但手术过程复杂,术后恢复期长,存在一定的手术风险,如感染、出血等。富血小板血浆(PRP)作为一种新的治疗方法,在骨缺损修复中显示出巨大的潜力。PRP中含有丰富的生长因子,如血小板源性生长因子(PDGF)、转化生长因子-β (TGF-β)、血管内皮生长因子(VEGF)等,可通过多种机制,如释放生长因子、促进血管生成、抑制炎症反应、募集活化细胞等机制,对骨缺损修复产生有益作用。对骨缺损的修复起到积极的作用,为骨组织的再生和修复提供有力的支持。
{"title":"Multimodal mechanisms of platelet-rich plasma in bone defect repair: Angiogenesis, inflammation modulation, and metabolic regulation","authors":"Junjie Chen ,&nbsp;Bo Liu ,&nbsp;Jiayang He ,&nbsp;Yuhao Wei ,&nbsp;Yuhan He ,&nbsp;Hang Zhou ,&nbsp;Zhiqiang Zhang ,&nbsp;Yiwen Weng ,&nbsp;Ming Cheng","doi":"10.1016/j.reth.2025.09.007","DOIUrl":"10.1016/j.reth.2025.09.007","url":null,"abstract":"<div><div>Bone defect is the loss of bone tissue due to trauma, fracture, infection, etc. This loss may lead to non-union of fracture, bone defect or bone deficiency, which seriously affects the patient's quality of life and even leads to dysfunction and disability. Although surgical repair is a common treatment modality, the surgical procedure is complicated, with a long postoperative recovery period and certain surgical risks, such as infection and bleeding. Platelet-rich plasma (PRP), as a novel therapeutic approach, has demonstrated remarkable potential in bone defect repair. PRP is rich in growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), etc., and can have a beneficial effect on bone defect repair through various mechanisms, such as the release of growth factors, the promotion of angiogenesis, the inhibition of inflammatory response, and the recruitment of activated cells and other mechanisms, which play a positive role in the repair of bone defects and provide strong support for the regeneration and repair of bone tissue.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 920-932"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319882","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
Corrigendum to ‘Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus’ [Regen Ther 30 (2025) 1–8] “在肝脏再生刺激下化学诱导的永酶无血血症大鼠肝祖细胞移植”的更正[Regen Ther 30 (2025) 1-8]
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-15 DOI: 10.1016/j.reth.2025.09.013
Masayuki Fukumoto, Akihiko Soyama, Daisuke Miyamoto, Takanobu Hara, Hajime Matsushima, Hajime Imamura, Mampei Yamashita, Tomohiko Adachi, Kengo Kanetaka, Susumu Eguchi
{"title":"Corrigendum to ‘Transplantation of chemically induced liver progenitors in Nagase analbuminemic rats under liver regenerative stimulus’ [Regen Ther 30 (2025) 1–8]","authors":"Masayuki Fukumoto,&nbsp;Akihiko Soyama,&nbsp;Daisuke Miyamoto,&nbsp;Takanobu Hara,&nbsp;Hajime Matsushima,&nbsp;Hajime Imamura,&nbsp;Mampei Yamashita,&nbsp;Tomohiko Adachi,&nbsp;Kengo Kanetaka,&nbsp;Susumu Eguchi","doi":"10.1016/j.reth.2025.09.013","DOIUrl":"10.1016/j.reth.2025.09.013","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Page 910"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319878","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
Bone morphogenetic protein-2-derived osteogenic peptide promotes bone regeneration via osteoblastogenesis 骨形态发生蛋白-2衍生成骨肽通过成骨细胞形成促进骨再生
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-15 DOI: 10.1016/j.reth.2025.09.006
Jong-Bin Lee , Ji-Youn Hong , Hyeeun Shim , Sehee Kim , Dong Won Lee , Bosun Kwon , Jeong-Ho Yun

Introduction

Bone morphogenetic protein (BMP)-2 plays a critical role in stimulating human mesenchymal stromal cells (hMSCs) differentiation, a key process in bone regeneration. However, the clinical application of BMP-2 has been hindered by several adverse effects. This study evaluated the effectiveness of a newly synthesized BMP2-derived osteogenic peptide (OP), which may overcome the limitations of BMP-2 while preserving its osteogenic potential.

Methods

OP5, selected from the OP family based on its osteogenic potential, was tested in vitro to compare its effects on osteogenic signaling, osteoblast differentiation, and hMSC gene expression in with those of BMP-2. New bone formation stimulated by OP5 or BMP-2 was assessed in vivo using radiographic and histological analyses in a rat model of calvarial defects.

Results

The optimal OP5 concentration of 1 μM supported hMSC viability and exhibited potent osteogenic activity. OP5 significantly activated BMP receptor types IA and II binding and the osteogenic protein kinase A and phosphorylated cAMP response element-binding protein signaling pathway. OP5-induced gene expressions of alkaline phosphatase and osteocalcin peaked on day 4 (early osteogenesis) and were sustained until day 14 (late osteogenesis). In vivo, 100 μg OP5 demonstrated superior bone formation compared to other doses (50, 300, and 600 μg), but was less effective than BMP-2. The amount of bone regeneration varied with different doses of OP5.

Conclusions

OP5, a low-molecular-weight peptide with strong osteogenic potential, may be a viable alternative to BMP-2 for clinical bone regeneration, minimizing BMP2-associated adverse effects.
骨形态发生蛋白(BMP)-2在刺激人间充质间质细胞(hMSCs)分化中起关键作用,这是骨再生的关键过程。然而,BMP-2的临床应用一直受到一些不良反应的阻碍。本研究评估了新合成的BMP-2衍生成骨肽(OP)的有效性,该肽可能克服BMP-2的局限性,同时保留其成骨潜能。方法从OP家族中选择具有成骨潜能的sop5进行体外检测,比较其与BMP-2对成骨信号传导、成骨细胞分化和hMSC基因表达的影响。在大鼠颅骨缺损模型中,通过x线摄影和组织学分析评估OP5或BMP-2刺激的新骨形成。结果1 μM的最佳OP5浓度支持hMSC的存活,并表现出较强的成骨活性。OP5显著激活BMP受体IA型和II型结合以及成骨蛋白激酶A和磷酸化cAMP反应元件结合蛋白信号通路。op5诱导的碱性磷酸酶和骨钙素基因表达在第4天(早期成骨)达到峰值,并持续到第14天(晚期成骨)。在体内,与其他剂量(50、300和600 μg)相比,100 μg的OP5表现出更好的骨形成,但效果不如BMP-2。不同剂量OP5对骨再生的影响不同。结论sop5是一种具有较强成骨潜能的低分子量肽,可作为BMP-2的替代品用于临床骨再生,减少BMP-2相关的不良反应。
{"title":"Bone morphogenetic protein-2-derived osteogenic peptide promotes bone regeneration via osteoblastogenesis","authors":"Jong-Bin Lee ,&nbsp;Ji-Youn Hong ,&nbsp;Hyeeun Shim ,&nbsp;Sehee Kim ,&nbsp;Dong Won Lee ,&nbsp;Bosun Kwon ,&nbsp;Jeong-Ho Yun","doi":"10.1016/j.reth.2025.09.006","DOIUrl":"10.1016/j.reth.2025.09.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Bone morphogenetic protein (BMP)-2 plays a critical role in stimulating human mesenchymal stromal cells (hMSCs) differentiation, a key process in bone regeneration. However, the clinical application of BMP-2 has been hindered by several adverse effects. This study evaluated the effectiveness of a newly synthesized BMP2-derived osteogenic peptide (OP), which may overcome the limitations of BMP-2 while preserving its osteogenic potential.</div></div><div><h3>Methods</h3><div>OP5, selected from the OP family based on its osteogenic potential, was tested <em>in vitro</em> to compare its effects on osteogenic signaling, osteoblast differentiation, and hMSC gene expression in with those of BMP-2. New bone formation stimulated by OP5 or BMP-2 was assessed <em>in vivo</em> using radiographic and histological analyses in a rat model of calvarial defects.</div></div><div><h3>Results</h3><div>The optimal OP5 concentration of 1 μM supported hMSC viability and exhibited potent osteogenic activity. OP5 significantly activated BMP receptor types IA and II binding and the osteogenic protein kinase A and phosphorylated cAMP response element-binding protein signaling pathway. OP5-induced gene expressions of alkaline phosphatase and osteocalcin peaked on day 4 (early osteogenesis) and were sustained until day 14 (late osteogenesis). <em>In vivo</em>, 100 μg OP5 demonstrated superior bone formation compared to other doses (50, 300, and 600 μg), but was less effective than BMP-2. The amount of bone regeneration varied with different doses of OP5.</div></div><div><h3>Conclusions</h3><div>OP5, a low-molecular-weight peptide with strong osteogenic potential, may be a viable alternative to BMP-2 for clinical bone regeneration, minimizing BMP2-associated adverse effects.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 911-919"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319749","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
Assessment of permeability in deep tissue capillaries using a new method reflects the nutrient supply status in a healthy heart 用一种新的方法评估深层组织毛细血管的通透性,反映了健康心脏的营养供应状况
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-14 DOI: 10.1016/j.reth.2025.10.005
Mio Nakamura , Yurika Yoshida-Kikkawa , Kousuke Sugiura , Yoko Itakura , Kensuke Ohse , Norihiko Sasaki , Yuzuru Ito , Masashi Toyoda

Introduction

The in vitro organoid model is a valuable tool for studying organ development and disease. However, a key current challenge is the absence of a functional vascular compartment, which results from limited understanding of capillary function in vivo. Multisystem disorders involve physiological abnormalities that affect different organs in various ways. Notably, women have a higher prevalence of microvessel disease in the heart compared to men. This is because, until now, there has been no way to detect or evaluate the material exchange functions carried out by capillaries deep within healthy heart tissue.

Methods

To detect fluorescent material leaking from intracardiac microvessels deep within the left ventricular wall under healthy conditions, female mice were injected with fluorescent dextran via the tail vein. The heart tissue was quickly removed, frozen, sliced, and examined directly under fluorescence. Additionally, the extent of the fluorescent substance diffusion was measured in young and aged female mice.

Results

We observed fluorescent substances leaking from deep heart capillaries under healthy conditions. We then developed a method to measure capillary permeability by assessing the diffusion area. Furthermore, this method showed that the permeability of capillaries in the hearts of aged female mice was lower than that of young female mice.

Conclusion

We have developed a method to assess capillary permeability in deep tissue. This research will improve our understanding of how capillaries exchange substances and support tissue function. This new method will not only provide new insights into studies of cardiac disease risk and sex differences, but also assist in developing more advanced in vitro models. It will further aid in refining the best cell transplantation techniques.
体外类器官模型是研究器官发育和疾病的重要工具。然而,目前的一个关键挑战是缺乏功能性血管室,这是由于对体内毛细血管功能的了解有限造成的。多系统疾病包括以各种方式影响不同器官的生理异常。值得注意的是,与男性相比,女性心脏微血管疾病的患病率更高。这是因为,到目前为止,还没有办法检测或评估健康心脏组织深处毛细血管所执行的物质交换功能。方法在健康状态下,雌性小鼠经尾静脉注射荧光葡聚糖,检测左室壁深处心内微血管渗漏的荧光物质。迅速取出心脏组织,冷冻,切片,并在荧光下直接检查。此外,还测量了荧光物质在年轻和老年雌性小鼠中的扩散程度。结果在健康状态下,心脏深层毛细血管有荧光物质渗漏。然后,我们开发了一种通过评估扩散面积来测量毛细管渗透率的方法。此外,该方法还显示老年雌性小鼠心脏毛细血管通透性低于年轻雌性小鼠。结论建立了一种评价深部组织毛细血管通透性的方法。这项研究将提高我们对毛细血管交换物质和支持组织功能的理解。这种新方法不仅将为心脏病风险和性别差异的研究提供新的见解,而且还有助于开发更先进的体外模型。这将进一步帮助完善最好的细胞移植技术。
{"title":"Assessment of permeability in deep tissue capillaries using a new method reflects the nutrient supply status in a healthy heart","authors":"Mio Nakamura ,&nbsp;Yurika Yoshida-Kikkawa ,&nbsp;Kousuke Sugiura ,&nbsp;Yoko Itakura ,&nbsp;Kensuke Ohse ,&nbsp;Norihiko Sasaki ,&nbsp;Yuzuru Ito ,&nbsp;Masashi Toyoda","doi":"10.1016/j.reth.2025.10.005","DOIUrl":"10.1016/j.reth.2025.10.005","url":null,"abstract":"<div><h3>Introduction</h3><div>The <em>in vitro</em> organoid model is a valuable tool for studying organ development and disease. However, a key current challenge is the absence of a functional vascular compartment, which results from limited understanding of capillary function <em>in vivo</em>. Multisystem disorders involve physiological abnormalities that affect different organs in various ways. Notably, women have a higher prevalence of microvessel disease in the heart compared to men. This is because, until now, there has been no way to detect or evaluate the material exchange functions carried out by capillaries deep within healthy heart tissue.</div></div><div><h3>Methods</h3><div>To detect fluorescent material leaking from intracardiac microvessels deep within the left ventricular wall under healthy conditions, female mice were injected with fluorescent dextran via the tail vein. The heart tissue was quickly removed, frozen, sliced, and examined directly under fluorescence. Additionally, the extent of the fluorescent substance diffusion was measured in young and aged female mice.</div></div><div><h3>Results</h3><div>We observed fluorescent substances leaking from deep heart capillaries under healthy conditions. We then developed a method to measure capillary permeability by assessing the diffusion area. Furthermore, this method showed that the permeability of capillaries in the hearts of aged female mice was lower than that of young female mice.</div></div><div><h3>Conclusion</h3><div>We have developed a method to assess capillary permeability in deep tissue. This research will improve our understanding of how capillaries exchange substances and support tissue function. This new method will not only provide new insights into studies of cardiac disease risk and sex differences, but also assist in developing more advanced <em>in vitro</em> models. It will further aid in refining the best cell transplantation techniques.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 900-909"},"PeriodicalIF":3.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319877","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
Functionalization of 3D printed PLGA-based scaffolds for bone regeneration 基于plga的3D打印骨再生支架功能化研究
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-13 DOI: 10.1016/j.reth.2025.10.003
Xuan Yan , Yanhua Wei , Yicai Luo , Ziwei Wu , Zhe Liu , Hongbing Liao
Bone defect remains an intractable issue for clinical orthopedics owing to their varied sizes and irregular shapes. Poly (lactic acid-co-glycolic acid) (PLGA)-based artificial bone grafts has garnered considerable attention in bone repair owing to their outstanding biocompatibility and tunable biodegradability. 3D printing technology is a feasible means due to its ability to construct scaffolds with defined shapes for restoring bone defects in clinical practice. In this review, the physicochemical properties of PLGA and 3D printing technology are briefly introduced. In addition, diverse strategies to improve the osteogenic performance of 3D printed PLGA scaffolds are elaborated. Finally, current challenges and future perspectives of 3D printed PLGA scaffolds applied in clinical practice are proposed.
骨缺损由于其大小不一、形状不规则,一直是骨科临床的难题。聚乳酸-羟基乙酸(PLGA)为基础的人工骨由于其优异的生物相容性和可调节的生物降解性在骨修复中引起了广泛的关注。3D打印技术能够构建具有特定形状的支架用于骨缺损修复,在临床实践中是一种可行的手段。本文简要介绍了PLGA的理化性质和3D打印技术。此外,还阐述了提高3D打印PLGA支架成骨性能的多种策略。最后,提出了3D打印PLGA支架在临床应用中面临的挑战和未来的展望。
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引用次数: 0
Primed human pluripotent stem cell-derived blastocyst-like cell aggregates with partial lineage specification 引物人类多能干细胞衍生的囊胚样细胞聚集体与部分谱系规范
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-13 DOI: 10.1016/j.reth.2025.10.007
Kaori Mutsuda-Zapater , Xiaopeng Wen , Satoshi Imamura , Shiho Terada , Kyoko Sawada , Kei Saito , Ken-ichiro Kamei

Introduction

Human blastoids, blastocyst-like structures assembled in vitro, hold great promise for decoding the earliest steps of human development. However, most existing protocols rely on naïve human pluripotent stem cells (hPSCs), which are chromosomally unstable and technically demanding.

Methods

We developed a method to generate human blastocyst-like cell aggregates directly from primed hPSCs using a thermoresponsive hydrogel. Generated blastocyst-like cell aggregates were evaluated for morphological features, lineage marker expression via immunocytochemistry, transcriptional profiles using single-cell RNA sequencing, and functional capacity through in vitro implantation assays.

Results

Primed hPSC-derived blastocyst-like cell aggregates recapitulated key morphological features of human blastocysts, including cyst formation and spatial expression of epiblast, trophectoderm, and primitive endoderm markers. Single-cell RNA sequencing revealed that a subset of cells showed transcriptional profiles resembling epiblast-, trophectoderm-, and primitive endoderm-like cells although a substantial proportion remained undifferentiated. Functionally, blastocyst-like cell aggregates demonstrated in vitro implantation potential, trophoblast differentiation, and secretion of human chorionic gonadotropin.

Conclusions

This work introduces a more accessible platform for generating human blastocyst-like cell aggregates from primed hPSCs, broadening their utility for investigating early development events. Insights gained from blastocyst-like cell aggregates have the potential to advance the modelling of early-onset diseases, drive innovations in regenerative therapies, and contribute to the development of assisted reproductive technologies.
人类胚泡,即体外组装的囊胚样结构,在解码人类发育的最初阶段方面有着巨大的希望。然而,大多数现有的方案依赖于naïve人类多能干细胞(hPSCs),这是染色体不稳定和技术要求高。方法建立了一种利用热反应性水凝胶直接从引物的hPSCs中生成人囊胚样细胞聚集体的方法。通过免疫细胞化学评估生成的囊胚样细胞聚集体的形态特征、谱系标记表达、单细胞RNA测序的转录谱和体外植入试验的功能能力。结果衍生的胚泡样细胞聚集体重现了人胚泡的主要形态学特征,包括囊的形成和外胚层、滋养外胚层和原始内胚层标记物的空间表达。单细胞RNA测序显示,一部分细胞表现出类似外胚层、滋养外胚层和原始内胚层样细胞的转录谱,尽管很大一部分细胞仍未分化。在功能上,囊胚样细胞聚集体表现出体外植入潜力、滋养细胞分化和人绒毛膜促性腺激素的分泌。本研究为从引物的人造血干细胞中生成人囊胚样细胞聚集体提供了一个更容易获得的平台,扩大了其在研究早期发育事件中的应用范围。从囊胚样细胞聚集体中获得的见解有可能推进早发性疾病的建模,推动再生疗法的创新,并有助于辅助生殖技术的发展。
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引用次数: 0
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Regenerative Therapy
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