Regenerative Therapy最新文献_第4页

From scaffold to function: A systematic review on dLECM-based hydrogels for liver tissue engineering — Fabrication, properties, and translational applications 从支架到功能：基于dlecm的肝组织工程水凝胶的系统综述-制备，性能和转化应用

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-18 DOI: 10.1016/j.reth.2025.11.006

Ziba Majidi , Mohammad Mahdi Sarvi , Mohammad Aref Rajabi , Houran Firouzian , Iman Seyhoun , Masoumeh Majidi Zolbin

<div><h3>Background</h3><div>Liver tissue engineering is a rapidly advancing field aiming to address the critical shortage of donor organs and improve <em>in vitro</em> models for drug screening and disease modeling. Decellularized liver extracellular matrix (dLECM)-based hydrogels have emerged as a leading biomaterial platform due to their ability to preserve the native biochemical composition, microstructure, and biomechanical cues of the liver microenvironment. This systematic review aims to comprehensively evaluate the methodologies, physicochemical properties, biological performance, and translational applications of dLECM-derived hydrogels in liver tissue engineering, with a focus on fabrication protocols, functional outcomes, and challenges toward clinical implementation.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in accordance with PRISMA 2020 guidelines across PubMed, Scopus, Google scholar and Web of Science. A total of 74 studies were included after screening 536 records identified from databases. Data were extracted on tissue source, decellularization techniques, dECM solubilization, hydrogel formulation, crosslinking methods, physicochemical characterization, and <em>in vitro</em>/<em>in vivo</em> functional outcomes.</div></div><div><h3>Results</h3><div>The majority of studies utilized porcine or rodent livers, with immersion/agitation and vascular perfusion as the primary decellularization methods. Sodium dodecyl sulfate (SDS), Triton X-100, and ammonium hydroxide were the most common detergents, often combined with enzymatic treatments (e.g., DNase, trypsin) to enhance nuclear removal. dLECM was predominantly solubilized using pepsin in acidic conditions (acetic acid or HCl) and reconstituted into hydrogels via thermal gelation at 37 °C. The resulting hydrogels demonstrated excellent biocompatibility, supporting high viability and enhanced functional activity—including albumin secretion, urea synthesis, and expression of hepatic markers (e.g., CYP450, CK18, AFP)—in primary hepatocytes, HepG2 cells, and stem cell-derived hepatocyte-like cells. Advanced applications such as 3D bioprinting, organoid culture, and <em>in vivo</em> transplantation in liver injury models (e.g., CCl<sub>4</sub>-induced fibrosis, acute liver failure) further highlight the therapeutic potential of these biomaterials. However, significant heterogeneity was observed in decellularization efficacy, residual DNA content (ranging from 1.04 % to 21.74 ng/mg), and mechanical characterization, with many studies lacking standardized reporting of storage modulus (G′) or gelation kinetics.</div></div><div><h3>Conclusion</h3><div>dLECM-based hydrogels represent a highly promising and biomimetic platform for liver tissue engineering, capable of supporting complex cellular functions and regenerative outcomes. Despite significant progress, standardization of fabrication protocols, comprehensive physicochemical characterization, and long-term <em

肝组织工程是一个快速发展的领域，旨在解决供体器官的严重短缺，改善药物筛选和疾病建模的体外模型。基于脱细胞肝细胞外基质（dLECM）的水凝胶已成为一种领先的生物材料平台，因为它们能够保留肝脏微环境的天然生化成分、微观结构和生物力学线索。本系统综述旨在全面评估dlecm衍生水凝胶在肝组织工程中的方法、物理化学性质、生物性能和转化应用，重点关注制备方案、功能结果和临床实施面临的挑战。方法按照PRISMA 2020指南，在PubMed、Scopus、谷歌scholar和Web of Science中进行系统检索。从数据库中筛选536条记录后，共纳入74项研究。提取组织来源、脱细胞技术、dECM增溶、水凝胶配方、交联方法、理化表征和体外/体内功能结果的数据。结果大多数研究使用猪或啮齿动物肝脏，以浸泡/搅拌和血管灌注作为主要的脱细胞方法。十二烷基硫酸钠（SDS）， Triton X-100和氢氧化铵是最常见的洗涤剂，通常与酶处理（如DNase，胰蛋白酶）联合使用以增强核去除。dLECM主要用胃蛋白酶在酸性条件下（醋酸或盐酸）溶解，并在37℃下通过热凝胶重组成水凝胶。所得水凝胶在原代肝细胞、HepG2细胞和干细胞衍生的肝细胞样细胞中表现出优异的生物相容性，支持高活力和增强的功能活性，包括白蛋白分泌、尿素合成和肝脏标志物（如CYP450、CK18、AFP）的表达。3D生物打印、类器官培养和肝损伤模型（如ccl4诱导的纤维化、急性肝衰竭）的体内移植等先进应用进一步凸显了这些生物材料的治疗潜力。然而，在脱细胞效果、残留DNA含量（1.04%至21.74 ng/mg）和力学特性方面观察到显著的异质性，许多研究缺乏存储模量（G '）或凝胶动力学的标准化报告。结论基于lecm的水凝胶是一种非常有前途的肝脏组织工程仿生平台，能够支持复杂的细胞功能和再生结果。尽管取得了重大进展，但标准化的制造方案、全面的物理化学表征和长期的体内安全性评估是推动这些材料走向临床转化的关键。

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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 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-17 DOI: 10.1016/j.reth.2025.11.008

Anna Arita , Yoshitomo Saita , Naho Fujiwara , Yasuhiro Homma , Morikuni Tobita

Introduction

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.

Methods

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 Staphylococcus aureus, Streptococcus spp., Cutibacterium acnes, Micrococcus spp., Bacillus subtilis, and Candida albicans.

Results

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 10²–10³ colony forming units (cfu)/mL or higher. While C. albicans could not be detected separately from non-specific PRP signals using FCM, it was detectable in PPP at ≥10² 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.

Conclusion

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.

富血小板血浆（PRP）广泛用于缓解疼痛、伤口愈合等方面。然而，最近的报告记录了PRP治疗后发生的感染病例。在本研究中，我们旨在研究与PRP治疗相关的潜在微生物污染风险，并评估适合临床使用的快速微生物检测方法。方法评估采血、PRP制备和无菌检验过程中微生物污染的风险。为了评估合适的检测方法，我们比较了流式细胞术（FCM）和聚合酶链反应（PCR）检测PRP中微生物污染的灵敏度。为此，PRP样品接种了金黄色葡萄球菌、链球菌、痤疮表皮杆菌、微球菌、枯草芽孢杆菌和白色念珠菌。结果经皮肤消毒后，10例患者中有6例在静脉穿刺部位检出微生物菌落。环境监测在三个匿名PRP制备设施中的两个发现了空气中微生物菌落。不育试验显示85例残余PRP和15例血小板不全血浆（PPP）均为阴性。在菌落形成单位(cfu)/mL或更高的浓度下，FCM检测PRP微生物的灵敏度是有效的。虽然白色念珠菌不能与非特异性PRP信号分开使用FCM检测，但在PPP≥102 cfu/mL时可检测到。当分析纯微生物悬浮液时，PCR检测微生物的灵敏度很好，然而，当PRP样品中含有某些微生物菌株时，它产生假阴性和假阳性结果的比率很高。结论静脉穿刺和PRP生产过程中均存在微生物污染风险。为了减少这些风险，可能有必要改进静脉穿刺地点的消毒方案和采血方法，并实施适当的设施特定措施。虽然需要进一步提高检测灵敏度，但FCM是一种很有前途的检测PRP中活菌的方法。鉴于微生物污染不能完全消除，提供PRP治疗的临床医生应对术后感染的可能性保持警惕，并确保建立适当的随访方案。

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引用次数: 0

IFNγ and TNFα optimize salivary gland mesenchymal stromal cells: an alternative to marrow- and adipose-MSCs for radiation xerostomia. IFNγ和TNFα优化唾液腺间充质间质细胞：一种替代骨髓和脂肪间充质间质细胞治疗放射性口干症。

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-14 eCollection Date: 2025-12-01 DOI: 10.1016/j.reth.2025.11.004

Michele C Larsen, Ilya Gurevic, Liliana Berube, Addie Vande Loo, Elizabeth Hanson, Ryan Adam, Valeria Manfrè, Maxwell Parker, Cristina Paz, Jacques Galipeau, Randall J Kimple, Grace Blitzer, Sara S McCoy

Objectives: Local mesenchymal stromal cell (MSC) administration is a promising therapy for xerostomia. MSCs deploy their advantageous effects through their trophic secretome and immunomodulatory capabilities. These functions are enhanced with IFNγ pre-licensing, but the effects of TNFα pre-licensing are unknown. Our objective was to compare MSCs by tissue source (MSC(BM), MSC(AD), and salivary gland-derived [MSC(SG)]) and by cytokine pre-licensing conditions.

Methods: We used single cell and bulk RNA sequencing and ELISA to determine key trophic and immunomodulatory features differing between human MSC(BM), MSC(AD), and MSC(SG). We used ELISA and flow cytometry of T-cell co-culture to define the effect of IFNγ and/or TNFα on MSC trophic secretome and immunomodulatory capacity. Finally, we studied salivary flow and glandular recovery with MSC injection in radiation-induced xerostomia mice.

Results: Bulk RNA sequencing (RNAseq) of MSC(BM), MSC(AD), and MSC(SG) revealed that they shared 85 % of transcripts. Key differences included extracellular matrix production and response to cytokines in MSC(SG). Single cell RNA sequencing showed MSC(SG) treated with IFNγ and TNFα transcriptionally diverged from other treatment conditions. Regardless of MSC source, dual stimulation of MSCs with IFNγ and TNFα produced an average of more than a 20-fold increase in R-Spondin 3 compared to vehicle conditions. Additionally, IFNγ and TNFα pre-licensing optimized immunomodulatory marker expression more than IFNγ alone. Intercellular adhesion molecule 1 increased 12-fold more, programmed death ligand 1 increased 1.4-fold more, and indoleamine 2,3 dioxygenase increased 2-fold more with IFNγ/TNFα pre-licensing than IFNγ alone. Both cytokine stimulation conditions resulted in a 1.2-fold decrease in T-cell proliferation. Gland structure, aquaporin 5, and salivary flow are preserved in irradiated mice treated with MSC(SG) pre-licensed with IFNγ/TNFα.

Conclusion: MSC(SG) pre-licensed with both IFNγ and TNFα deploy advantageous functional cell attributes for salivary gland regenerative medicine.

目的：局部间充质间质细胞（MSC）给药是治疗口干症的一种很有前途的治疗方法。MSCs通过其营养分泌组和免疫调节能力发挥其优势作用。ifn - γ预许可可增强这些功能，但tnf - α预许可的影响尚不清楚。我们的目标是通过组织来源(MSC（BM)， MSC（AD）和唾液腺来源[MSC(SG)]）和细胞因子预许可条件来比较MSCs。方法：采用单细胞和大体积RNA测序和ELISA法测定人间充质干细胞（BM）、间充质干细胞（AD）和间充质干细胞（SG）之间不同的关键营养和免疫调节特征。我们使用ELISA和t细胞共培养的流式细胞术来确定IFNγ和/或TNFα对MSC营养分泌组和免疫调节能力的影响。最后，我们研究了骨髓间充质干细胞注射对辐射致口干小鼠唾液流动和腺体恢复的影响。结果：MSC(BM)， MSC（AD）和MSC（SG）的Bulk RNA测序（RNAseq）显示它们共享85%的转录本。主要差异包括MSC（SG）的细胞外基质生成和对细胞因子的反应。单细胞RNA测序显示，IFNγ和TNFα处理的MSC（SG）在转录上与其他处理条件不同。无论骨髓间充质干细胞的来源如何，IFNγ和TNFα对骨髓间充质干细胞的双重刺激产生的R-Spondin 3平均比载药条件增加20倍以上。此外，IFNγ和TNFα预先许可比单独使用IFNγ更能优化免疫调节标志物的表达。细胞间粘附分子1增加了12倍，程序性死亡配体1增加了1.4倍，吲哚胺2,3双加氧酶增加了2倍，IFNγ/TNFα预许可比单独使用IFNγ多。两种细胞因子刺激条件导致t细胞增殖减少1.2倍。经ifn - γ/ tnf - α预先许可的MSC（SG）辐照小鼠的腺体结构、水通道蛋白5和唾液流量得以保留。结论：IFNγ和TNFα预先许可的MSC（SG）在唾液腺再生医学中具有优势的功能细胞属性。

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引用次数: 0

Cell-based regenerative therapy for retinal diseases: challenges and emerging bioengineering strategies. 视网膜疾病的细胞再生治疗：挑战和新兴的生物工程策略。

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-14 eCollection Date: 2025-12-01 DOI: 10.1016/j.reth.2025.11.002

Yasuaki Iwama, Tomohiro Masuda, Ava Maeyama, Kevin T Eade, Martin Friedlander, Kohji Nishida, Michiko Mandai

Cell-based regenerative therapy holds promise for a broad spectrum of retinal diseases characterized by irreversible photoreceptor cell (PRC) loss, including retinitis pigmentosa (RP) and age-related macular degeneration. While gene therapy has delivered landmark successes for selected indications, it does not directly replace lost PRCs and is not well suited for advanced-stages of diseases. In this context, cell-based regenerative approaches-either PRC suspensions or retinal sheets-aim to rebuild the outer retinal circuitry and restore light responses across different retinal diseases. In addition to its relatively high prevalence (1 in 3000-5000 individuals), the PRC-specific degeneration pattern in RP has motivated numerous preclinical studies aimed at clinical application. In this review, we first outline the two major graft modalities-cell suspensions and retinal sheet transplantation-from the perspective of their respective advantages and limitations. Here, we summarize preclinical and clinical evidence for both modalities, highlighting the first-in-human trial of transplantation of human iPSC-derived retinal organoid sheets in late-stage RP, which demonstrated a favorable safety profile and two-year graft survival. We then analyze the challenges that emerged from this first-in-human trial and discuss potential bioengineering and biological solutions. Finally, we consider the prospects of extending these transplantation strategies beyond RP to macular diseases, where PRC replacement may also provide therapeutic benefit. Collectively, the field is transitioning from proof-of-concept to diversified clinical exploration; converging advances in developmental biology, genome engineering, and high-throughput cell analytics are poised to accelerate functional vision restoration in retinal diseases.

基于细胞的再生疗法有望治疗以不可逆感光细胞（PRC）丧失为特征的广泛的视网膜疾病，包括视网膜色素变性（RP）和年龄相关性黄斑变性。虽然基因疗法在特定适应症方面取得了里程碑式的成功，但它并不能直接替代丢失的prc，也不太适合晚期疾病。在这种情况下，基于细胞的再生方法——PRC悬液或视网膜薄片——旨在重建视网膜外回路并恢复不同视网膜疾病的光反应。除了其相对较高的患病率（3000-5000人中有1人）外，RP中prc特异性变性模式已经激发了许多旨在临床应用的临床前研究。在这篇综述中，我们首先从各自的优势和局限性的角度概述了两种主要的移植方式——细胞悬液和视网膜片移植。在这里，我们总结了这两种方式的临床前和临床证据，重点介绍了首次在晚期RP中移植人类ipsc衍生的视网膜类器官片的人体试验，该试验显示出良好的安全性和两年的移植存活率。然后，我们分析了首次人体试验中出现的挑战，并讨论了潜在的生物工程和生物学解决方案。最后，我们考虑将这些移植策略从RP扩展到黄斑疾病的前景，在黄斑疾病中，PRC替代也可能提供治疗益处。总的来说，该领域正在从概念验证过渡到多样化的临床探索；在发育生物学，基因组工程和高通量细胞分析的融合进展准备加速视网膜疾病的功能视力恢复。

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引用次数: 0

Fabrication and characterization of a multilayered PVA/alginate-diopside electrospun scaffold for tissue engineering applications. 用于组织工程的多层PVA/海藻酸盐-透辉糖电纺丝支架的制备和表征。

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-14 eCollection Date: 2025-12-01 DOI: 10.1016/j.reth.2025.10.009

Yuquan Jiang, S Baghaei

Introduction: One of the most effective methods for reproducing soft tissue is to apply multilayer soft tissue using the electrospinning technique, creating suitable conditions for wound healing.

Methods: In this study, a new bio-nanocomposite composition consisting of polyvinyl alcohol (PVA), alginate (ALG), and diopside nanoparticles with different weight percentages was used, employing the electrospun technique to create a homogenized fiber network. The PVA structure has a simple chemical structure with hydroxyl groups attached to the main chain, as not all acetate groups can be replaced with hydroxyl groups. To study the mechanical and biological properties of the samples, the tensile strength and biodegradation were investigated. Determination of fundamental groups, morphology, and phase analysis was performed using a Fourier-transform infrared spectrometer (FTIR), a scanning electron microscope (SEM), and an X-ray diffraction (XRD) technique. Also, the degree of hydrophilicity was measured in the water solution using a CCD camera. At all weight percentages, PVA is evenly distributed in the polymer medium. The nanofiber scaffolds prepared by the electrospinning method show porosity above 58 %.

Results: In general, due to the prolonged degradation of PVA and ALG, the study after three weeks reveals that significant weight changes have occurred in the samples containing the maximum amount of diopside nanoparticles. The FTIR analysis shows that the peaks corresponding to the C[bond, double bond]O, CH, and OH bonds remained unchanged. As a result, the absence of chemical interaction between PVA is proven. Tensile strength test showed that an increase in diopside nanoparticles disrupts the network chain and may lead to a decrease in the elastic modulus of the samples. The contact angle of the fiber arrangement was reduced from 151° to 121°, encompassing the lowest and highest amounts of diopside nanoparticles, respectively. According to the observations, the PVA nanocomposite scaffolds with 4 wt% diopside nanoparticles are suitable for soft texture engineering.

Conclusions: Nanocomposite scaffolds containing 4 wt% diopside nanoparticles have suitable conditions for cellular testing due to their mechanical, physical, and morphological properties.

摘要：利用静电纺丝技术制备多层软组织，为创面愈合创造适宜的条件，是软组织再生最有效的方法之一。方法：采用静电纺丝技术，将聚乙烯醇（PVA）、海藻酸盐（ALG）和透花苷纳米颗粒以不同的重量百分比组成一种新型的生物纳米复合材料，形成均匀的纤维网络。PVA结构的化学结构简单，主链上有羟基，因为不是所有的醋酸基团都可以被羟基取代。为了研究样品的力学和生物学性能，研究了样品的拉伸强度和生物降解。使用傅里叶变换红外光谱仪（FTIR）、扫描电子显微镜（SEM）和x射线衍射仪（XRD）技术进行基本基团的测定、形貌和物相分析。同时，用CCD相机测量了水溶液的亲水性。在所有重量百分比下，PVA均匀分布在聚合物介质中。静电纺丝法制备的纳米纤维支架的孔隙率在58%以上。结果：总的来说，由于PVA和ALG的降解时间较长，三周后的研究表明，含有最大量透辉石纳米颗粒的样品发生了明显的重量变化。FTIR分析表明，C[键，双键]O， CH和OH键对应的峰保持不变。结果证明PVA之间不存在化学相互作用。拉伸强度测试表明，透辉石纳米颗粒的增加破坏了网络链，可能导致样品的弹性模量下降。纤维排列的接触角从151°减小到121°，分别包含了最少和最多的透辉石纳米颗粒。结果表明，含4 wt%透辉石纳米颗粒的PVA纳米复合支架适用于软质结构工程。结论：含有4 wt%透花苷纳米颗粒的纳米复合支架具有良好的力学、物理和形态学性能。

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引用次数: 0

Generation of implant-type tissue-engineered cartilage from human embryonic stem cell-derived chondrocytes. 从人胚胎干细胞衍生的软骨细胞生成植入型组织工程软骨。

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-12 eCollection Date: 2025-12-01 DOI: 10.1016/j.reth.2025.10.012

Yen-Chih Huang, Hiroko Komura, Arhans Chairul Ismael, Yukiyo Asawa, Junlong Chen, Tomoyuki Kawasaki, Shin Enosawa, Hidenori Akutsu, Yasushi Fuchimoto, Kazuto Hoshi, Akihiro Umezawa, Makoto Komura

<p><strong>Introduction: </strong>Autologous cartilage transplantation has been applied clinically but its efficacy is limited by donor site morbidity, inter-donor variability, and high manufacturing costs. Primary chondrocytes also tend to dedifferentiate during expansion, which further limits their redifferentiation potential. Cartilage is weakly immunogenic and is thus an ideal tissue source for allogeneic transplantation. Allogeneic transplantation has drawn much interest due to the immune-privileged nature of cartilage and the recent success of allogeneic chondrocyte therapies. Meanwhile, human embryonic stem cells (hESCs) offer a scalable source of chondrocytes with high redifferentiation capacity. Building on the xeno-free automated chondrogenic differentiation of SEES2 hESCs in previous research, this study aims to establish an implant-type regenerative cartilage platform using hESCs for potential allogeneic transplantation.</p><p><strong>Methods: </strong>hESCs (SEES2) were differentiated into cartilage tissue using an embryoid body-based protocol and cultured on collagen-coated dishes for 60 days. Cartilage-derived chondrocytes were isolated and expanded in a monolayer. Passage 3 (P3) cells were used for pellet culture, maintained for 21 days, and analyzed using histology and biochemical assays. Gene expression was assessed by RNA sequencing. Additionally, P3 chondrocytes were seeded onto bioresorbable PGA nonwoven fabric scaffolds, implanted subcutaneously into athymic nude mice for 4 weeks, and subjected to histological and biochemical analyses.</p><p><strong>Results: </strong>Human embryonic stem cell-derived chondrocytes (hESC-Chs) were successfully isolated and expanded over 10<sup>14</sup>-fold cumulatively. They expressed chondrogenic markers that were comparable to those of human auricular chondrocytes (hACs) and lacked pluripotency-associated genes. In pellet culture, hESC-Chs produced cartilage matrix, which was less robust than that produced by hACs. RNA sequencing showed overall similarity between groups, and extracellular matrix-related genes such as CHI3L1 and HAS3 were upregulated in hACs. In scaffold-based constructs, hESC-Chs exhibited inferior matrix production at low density (5.0 × 10<sup>7</sup> cells/cm<sup>3</sup>) but showed improved glycosaminoglycan and type II collagen deposition at high density (2.0 × 10<sup>8</sup> cells/cm<sup>3</sup>), reaching levels equivalent to those of hACs under high-density conditions. Notably, PD-L1 expression was elevated in hESC-Chs, indicating their potential immunomodulatory properties.</p><p><strong>Conclusion: </strong>We successfully established a reproducible method for isolating and expanding chondrocytes from hESC-derived cartilage tissue. Under optimized culture conditions, these cells demonstrated the capacity for redifferentiation and <i>in vivo</i> cartilage regeneration, highlighting their potential as a stable and scalable allogeneic cell source for cartilage repair.

自体软骨移植已在临床上应用，但其疗效受到供体部位发病率、供体间变异性和制造成本高的限制。原代软骨细胞在扩张过程中也倾向于去分化，这进一步限制了它们的再分化潜力。软骨是弱免疫原性的，因此是异体移植的理想组织来源。由于软骨的免疫特性和最近同种异体软骨细胞治疗的成功，同种异体移植引起了人们的极大兴趣。同时，人类胚胎干细胞（hESCs）提供了一种可扩展的软骨细胞来源，具有高再分化能力。本研究在前人研究的无xeno诱导的SEES2 hESCs自动成软骨分化的基础上，旨在利用hESCs建立一种可用于潜在同种异体移植的植入型再生软骨平台。方法：采用类胚体方法将hESCs （SEES2）分化为软骨组织，在胶原包被培养皿中培养60 d。软骨来源的软骨细胞被分离并扩展成单层。传代3 （P3）细胞进行微球培养，保存21天，进行组织学和生化分析。通过RNA测序评估基因表达。将P3软骨细胞植入生物可吸收的PGA无纺布支架上，皮下植入胸腺裸鼠4周，进行组织学和生化分析。结果：成功分离出人胚胎干细胞衍生软骨细胞（hESC-Chs），并累积扩增超过1014倍。它们表达的软骨形成标志物与人耳软骨细胞（hACs）相似，缺乏多能性相关基因。在微球培养中，hESC-Chs产生的软骨基质不如hACs产生的软骨基质健壮。RNA测序显示各组之间总体相似，细胞外基质相关基因如CHI3L1和HAS3在hACs中上调。在基于支架的构建中，hESC-Chs在低密度条件下（5.0 × 107细胞/cm3）基质生成较差，但在高密度条件下（2.0 × 108细胞/cm3），糖胺聚糖和II型胶原沉积得到改善，达到与高密度条件下hACs相当的水平。值得注意的是，PD-L1在hESC-Chs中的表达升高，表明它们具有潜在的免疫调节特性。结论：我们成功建立了一种可重复性的从hesc来源软骨组织中分离和扩增软骨细胞的方法。在优化的培养条件下，这些细胞显示出再分化和体内软骨再生的能力，突出了它们作为软骨修复的稳定和可扩展的同种异体细胞来源的潜力。

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引用次数: 0

Erratum to "Assessment of permeability in deep tissue capillaries using a new method reflects the nutrient supply status in a healthy heart" [Regen Ther, 30C (2025), 1019]. “一种评估深层组织毛细血管通透性的新方法反映健康心脏的营养供应状况”的勘误[Regen Ther， 30C(2025), 1019]。

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-11 eCollection Date: 2025-12-01 DOI: 10.1016/j.reth.2025.11.001

Mio Nakamura, Yurika Yoshida-Kikkawa, Kousuke Sugiura, Yoko Itakura, Kensuke Ohse, Norihiko Sasaki, Yuzuru Ito, Masashi Toyoda

[This corrects the article DOI: 10.1016/j.reth.2025.10.005.].

[这更正了文章DOI: 10.1016/j.reth.2025.10.005.]。

引用次数: 0

The feasibility of human embryonic stem cell (hESC)-derived cartilage for tracheoplasty. 人胚胎干细胞（hESC）衍生软骨用于气管成形术的可行性。

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-10 eCollection Date: 2025-12-01 DOI: 10.1016/j.reth.2025.11.005

Makoto Komura, Junlong Chen, Hiroko Komura, Ren Itou, Shin Enosawa, Kazuto Hoshi, Yasushi Fuchimoto, Hidenori Akutsu, Akihiro Umezawa

Introduction: Airway reconstruction with autologous costal cartilage often results in long-term complications. On the other hand, implant-type regenerated cartilage using chondrocytes and scaffolds is associated with better biocompatibility and outcomes. Nevertheless, obtaining a substantial amount of chondrocytes remains a challenge. Allogenic cartilage from human embryonic stem cells (hESCs) can be used as an alternative graft for tracheal reconstruction. The aim of this study was to determine the regenerative potential of hESCs-derived cartilage tissue.

Methods: The clinical grade hESC line sSEES-2 was cultured in chondrocyte differentiation media for eight weeks. Maturation potential was estimated by subcutaneous transplantation into immunodeficient mice and the mechanical properties were measured with a tactile sensor. For tracheoplasty studies, the matured cartilage constructs were implanted into tracheotomized sites in athymic rats, and were evaluated 1- and 3-months post-implantation through endoscopy and histological analysis.

Results: Small cartilage tissues - or "cartilage islets" - were successfully obtained by culturing the SEES2 cells in specialized media. The thickness and strength (Young's modulus) of the grafted cartilage increased one month after implantation, indicating maturation. Furthermore, the cartilage graft successfully restored artificial defects in rat trachea with no structural damage or air leakage. The tracheal mucosa recovered one month after the implantation, and airway patency was maintained for three months. Histological analysis of the tracheal tissues revealed epithelial regeneration, and direct integration between the cartilage graft and native cartilage without the formation of granulation tissue.

Conclusions: Cartilage tissue derived from hESCs successfully maintained airway structure and biocompatibility in a rat model for three months, which supports the application of engineered cartilage for clinical airway reconstruction.

自体肋软骨气道重建常导致长期并发症。另一方面，使用软骨细胞和支架的植入型再生软骨具有更好的生物相容性和预后。然而，获得大量软骨细胞仍然是一个挑战。来自人胚胎干细胞（hESCs）的同种异体软骨可以作为气管重建的替代移植物。本研究的目的是确定hescs来源的软骨组织的再生潜力。方法：临床级hESC细胞系sSEES-2在软骨细胞分化培养基中培养8周。通过免疫缺陷小鼠皮下移植估计成熟电位，并用触觉传感器测量力学性能。在气管成形术研究中，将成熟的软骨构建体植入胸腺大鼠的气管切开部位，并在植入后1个月和3个月通过内窥镜和组织学分析进行评估。结果：在专门培养基中培养SEES2细胞，成功获得小软骨组织或“软骨胰岛”。移植软骨的厚度和强度（杨氏模量）在植入1个月后增加，表明成熟。此外，软骨移植成功地修复了大鼠气管的人工缺损，无结构损伤和漏气现象。气管黏膜在植入1个月后恢复，气道通畅维持3个月。气管组织的组织学分析显示上皮再生，软骨移植物与天然软骨直接融合，没有形成肉芽组织。结论：hESCs软骨组织在大鼠模型中成功维持气道结构和生物相容性3个月，支持工程软骨在临床气道重建中的应用。

{"title":"The feasibility of human embryonic stem cell (hESC)-derived cartilage for tracheoplasty.","authors":"Makoto Komura, Junlong Chen, Hiroko Komura, Ren Itou, Shin Enosawa, Kazuto Hoshi, Yasushi Fuchimoto, Hidenori Akutsu, Akihiro Umezawa","doi":"10.1016/j.reth.2025.11.005","DOIUrl":"10.1016/j.reth.2025.11.005","url":null,"abstract":"<p><strong>Introduction: </strong>Airway reconstruction with autologous costal cartilage often results in long-term complications. On the other hand, implant-type regenerated cartilage using chondrocytes and scaffolds is associated with better biocompatibility and outcomes. Nevertheless, obtaining a substantial amount of chondrocytes remains a challenge. Allogenic cartilage from human embryonic stem cells (hESCs) can be used as an alternative graft for tracheal reconstruction. The aim of this study was to determine the regenerative potential of hESCs-derived cartilage tissue.</p><p><strong>Methods: </strong>The clinical grade hESC line sSEES-2 was cultured in chondrocyte differentiation media for eight weeks. Maturation potential was estimated by subcutaneous transplantation into immunodeficient mice and the mechanical properties were measured with a tactile sensor. For tracheoplasty studies, the matured cartilage constructs were implanted into tracheotomized sites in athymic rats, and were evaluated 1- and 3-months post-implantation through endoscopy and histological analysis.</p><p><strong>Results: </strong>Small cartilage tissues - or \"cartilage islets\" - were successfully obtained by culturing the SEES2 cells in specialized media. The thickness and strength (Young's modulus) of the grafted cartilage increased one month after implantation, indicating maturation. Furthermore, the cartilage graft successfully restored artificial defects in rat trachea with no structural damage or air leakage. The tracheal mucosa recovered one month after the implantation, and airway patency was maintained for three months. Histological analysis of the tracheal tissues revealed epithelial regeneration, and direct integration between the cartilage graft and native cartilage without the formation of granulation tissue.</p><p><strong>Conclusions: </strong>Cartilage tissue derived from hESCs successfully maintained airway structure and biocompatibility in a rat model for three months, which supports the application of engineered cartilage for clinical airway reconstruction.</p>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"1069-1073"},"PeriodicalIF":3.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12657384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The research landscape and trends of dental pulp stem cell studies (2010–2025): A bibliometric analysis 牙髓干细胞研究的研究前景和趋势（2010-2025）：文献计量学分析

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-04 DOI: 10.1016/j.reth.2025.10.021

Yu Zheng , Zhe Tang , Lu Li , Zheng Li

Background

Dental pulp stem cells (DPSCs) have emerged as a promising therapeutic modality in regenerative medicine, yet systematic bibliometric evaluation of global research landscape has been lacking.

Methods

Publications from 2010 to 2025 were retrieved from Web of Science Core Collection. After screening, 4599 English-language articles and reviews were analyzed using VOSviewer, CiteSpace, and Bibliometrix for publication trends, geographic distribution, author collaboration, journal characteristics, citation networks, and keyword co-occurrence.

Results

Global DPSC research demonstrated sustained growth, with annual publications increasing from 97 in 2010 to 464 in 2024. China (32.6 %), United States (15.9 %), and Japan (9.9 %) contributed over half the global output, though U.S. publications achieved higher citation impact. Sichuan University, Sun Yat-sen University, and Capital Medical University ranked highest in productivity. Author collaboration revealed interconnected clusters led by pioneering researchers including Shi Songtao, Nakashima Misako, and Nor Jacques E. Journal of Endodontics was the leading publishing platform, while co-citation analysis highlighted intellectual influence of multidisciplinary journals including Stem Cells, Biomaterials, and PNAS. Keyword analyses demonstrated thematic evolution from cellular characterization toward translational applications, with emerging frontiers focusing on extracellular vesicles, exosomes, and cell-free therapeutic strategies.

Conclusions

DPSC research has evolved into a mature, internationally collaborative scientific discipline successfully bridging fundamental biology and clinical application. A pivotal paradigm shift from cell-centric to cell-free therapies is currently underway. Future breakthroughs will likely depend on harnessing the DPSC secretome and developing intelligent, clinically viable regenerative strategies.

牙髓干细胞（DPSCs）已成为再生医学中一种很有前景的治疗方式，但缺乏对全球研究格局的系统文献计量评估。方法检索Web of Science Core Collection中2010 ~ 2025年发表的论文。筛选后，使用VOSviewer、CiteSpace和Bibliometrix对4599篇英文文章和评论进行了出版趋势、地理分布、作者合作、期刊特征、引文网络和关键词共现等方面的分析。结果全球DPSC研究持续增长，年发表论文从2010年的97篇增加到2024年的464篇。中国（32.6%）、美国（15.9%）和日本（9.9%）贡献了全球产出的一半以上，尽管美国出版物的引用影响力更高。四川大学、中山大学和首都医科大学的生产力排名最高。作者合作揭示了由石松涛、Nakashima Misako和Nor Jacques e等先驱研究人员领导的相互关联的集群，《牙髓学杂志》（Journal of Endodontics）是领先的出版平台，而共被引分析则突出了多学科期刊（包括Stem Cells、Biomaterials和PNAS）的学术影响力。关键词分析显示了从细胞表征到转化应用的主题演变，新兴前沿关注于细胞外囊泡、外泌体和无细胞治疗策略。结论sdpsc研究已发展成为一个成熟的、国际合作的科学学科，成功地连接了基础生物学和临床应用。从以细胞为中心到无细胞治疗的关键范式转变目前正在进行中。未来的突破可能取决于利用DPSC分泌组和开发智能，临床可行的再生策略。

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引用次数: 0

Mesenchymal stem cells in neurological disorders: Insights from clinical trials 神经系统疾病中的间充质干细胞：来自临床试验的见解

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2025-11-04 DOI: 10.1016/j.reth.2025.10.020

Beatriz Araújo , Inês Serrenho , Andreia Valente da Silva , Bragança Moisés Marceta , Graça Baltazar

Mesenchymal stem cells (MSCs) exhibit unique properties that make them promising candidates for cell therapy, particularly in neurological disorders. They can be derived from various tissues, with bone marrow, adipose tissue, umbilical cord, and placenta being the most common sources. Evidence suggests that the tissue of origin significantly influences MSC characteristics, including secretome composition, proliferation rate, and adhesion capacity.

Clinical trials have demonstrated the safety and therapeutic potential of MSCs in conditions such as spinal cord injury, multiple sclerosis, and stroke. MSC therapy has been associated with improvements in motor, sensory, and cognitive functions, as well as enhanced quality of life. Mechanistically, MSCs promote neuroprotection, reduce inflammation, and modulate immune responses. In spinal cord injury, intrathecal administration of adipose- and bone marrow-derived MSCs has led to significant functional recovery, with single high-dose treatments often yielding better outcomes than multiple lower doses. In amyotrophic lateral sclerosis, bone marrow-derived MSCs have shown potential in slowing disease progression, though higher doses do not always result in greater benefits. In multiple sclerosis, high doses of umbilical cord-derived MSCs improved quality of life and prevented disease progression, whereas lower doses of bone marrow-derived MSCs provided limited functional benefits.

While MSC therapy is considered safe, patient responses vary, and a definitive correlation between administered dose and therapeutic effects remains elusive. The small number of studies using comparable protocols impedes comparison of other relevant factor, limits the drawing of conclusions and underscore the importance of developing standardized protocols to optimize MSC-based treatments and maximize their clinical efficacy.

间充质干细胞（MSCs）表现出独特的特性，使其成为细胞治疗的有希望的候选者，特别是在神经系统疾病中。它们可以来自各种组织，骨髓、脂肪组织、脐带和胎盘是最常见的来源。有证据表明，来源组织显著影响间充质干细胞的特征，包括分泌组组成、增殖率和粘附能力。临床试验已经证明MSCs在脊髓损伤、多发性硬化症和中风等疾病中的安全性和治疗潜力。MSC治疗与运动、感觉和认知功能的改善以及生活质量的提高有关。在机制上，间充质干细胞促进神经保护，减少炎症，调节免疫反应。在脊髓损伤中，鞘内给予脂肪和骨髓来源的MSCs可显著恢复功能，单次高剂量治疗通常比多次低剂量治疗效果更好。在肌萎缩性侧索硬化症中，骨髓来源的MSCs显示出减缓疾病进展的潜力，尽管高剂量并不总是产生更大的益处。在多发性硬化症中，高剂量的脐带来源的MSCs改善了生活质量并预防了疾病进展，而低剂量的骨髓来源的MSCs提供了有限的功能益处。虽然骨髓间充质干细胞治疗被认为是安全的，但患者的反应各不相同，并且给药剂量和治疗效果之间的确切相关性仍然难以捉摸。使用可比较方案的研究数量较少，阻碍了其他相关因素的比较，限制了结论的得出，并强调了制定标准化方案以优化基于msc的治疗和最大化其临床疗效的重要性。

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引用次数: 0