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Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes. 益生菌衍生的 P8 蛋白:促进干细胞和角质形成细胞的增殖和迁移
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-11-04 DOI: 10.15283/ijsc24107
Soo Bin Jang, Yoojung Kim, Han Ceol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness. Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

益生菌对人体有各种不同的作用,并提供不同的健康益处。以前的报告表明,从鼠李糖乳杆菌中分离出来的 P8 蛋白(P8)具有抗癌特性。然而,其对干细胞和正常细胞的功效尚未见报道。在本研究中,我们评估了 P8 对细胞增殖和伤口愈合的影响,并研究了其潜在机制。根据划痕试验结果,我们证明了 P8 可通过激活细胞周期和促进干细胞干性,显著增加伤口愈合。通过在含有乳酸杆菌衍生的 P8 蛋白的培养基中培养干细胞,我们进一步研究了细胞机制,发现它能促进细胞增殖和迁移。此外,研究还发现P8能增强干性标志物(如OCT4和SOX2)的表达,并激活丝裂原活化蛋白激酶(MAPK)信号传导和Hippo通路。这些结果表明,P8能通过与MAPK和Hippo信号相关的方式增加干细胞增殖、迁移和干性,从而促进细胞生长。此外,P8 还能通过激活 MAPK 信号通路促进角质形成细胞的伤口愈合。这些结果表明,P8可能是通过激活细胞增殖来提高干细胞培养效率、增强皮肤病治疗效果的一种有前途的候选物质。
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引用次数: 0
Thermostable bFGF Improves Cell Lifespan by Enhancing Cell Activity in the Long-Term Culture of Human Orbicularis Oculi Stem Cells. 在人眼轮匝肌干细胞的长期培养过程中,恒温 bFGF 可通过增强细胞活性来延长细胞寿命。
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-10-23 DOI: 10.15283/ijsc24039
Geun-Ho Kang, Yeo Kyung Shin, Kyung Min Lim, Se Jong Kim, Myeongjin Song, Kwonwoo Song, Jung Hyun Kim, Dae Young Kim, Hang-Cheol Shin, Hyun Jin Shin, Ssang-Goo Cho

Stem cells derived from human orbicularis oculi muscle (hOOM) are a valuable resource for cell therapy. However, when stem cells are continuously cultured, their abilities tend to deteriorate over time. One method to address this issue is to use basic fibroblast growth factor (bFGF) to maintain the stem cell functionality. The limitation is that bFGF is unstable under mammalian cell culture conditions with a half-life of only 8 hours, which poses a significant challenge to the production and maintenance of high-quality stem cells. In this study, we used thermostable bFGF (TS-bFGF) and demonstrated that hOOM-derived stem cells cultured with TS-bFGF exhibited superior proliferation, stem cell function, reduced reactive oxygen species, and cellular senescence delay effect compared to cells cultured with wild-type bFGF. Considering the pivotal role of stem cells in broad ranges of applications such as regenerative medicine and cultured meat, we anticipate that TS-bFGF, owing to its thermostability and long-lasting properties, will contribute significantly to the acquisition of high-quality stem cells.

从人体眼轮匝肌提取的干细胞是细胞疗法的宝贵资源。然而,当干细胞被持续培养时,其能力往往会随着时间的推移而退化。解决这一问题的方法之一是使用碱性成纤维细胞生长因子(bFGF)来维持干细胞的功能。其局限性在于,碱性成纤维细胞生长因子在哺乳动物细胞培养条件下不稳定,半衰期仅为8小时,这对生产和维持高质量干细胞构成了巨大挑战。在这项研究中,我们使用了可恒温的bFGF(TS-bFGF),结果表明,与使用野生型bFGF培养的细胞相比,使用TS-bFGF培养的hOOM衍生干细胞在增殖、干细胞功能、活性氧减少和细胞衰老延缓效应等方面都表现得更为出色。考虑到干细胞在再生医学和养殖肉类等广泛应用中的关键作用,我们预计TS-bFGF因其热稳定性和长效特性,将为获得高质量干细胞做出重大贡献。
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引用次数: 0
Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics. 深度神经网络在间充质干细胞疗法制造过程中的应用。
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-09-26 DOI: 10.15283/ijsc24070
Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang

Current image-based analysis methods for monitoring cell confluency and status depend on individual interpretations, which can lead to wide variations in the quality of cell therapeutics. To overcome these limitations, images of mesenchymal stem cells cultured adherently in various types of culture vessels were captured and analyzed using a deep neural network. Among the various deep learning methods, a classification and detection algorithm was selected to verify cell confluency and status. We confirmed that the image classification algorithm demonstrates significant accuracy for both single- and multistack images. Abnormal cells could be detected exclusively in single-stack images, as multistack culture was performed only when abnormal cells were absent in the single-stack culture. This study is the first to analyze cell images based on a deep learning method that directly impacts yield and quality, which are important product parameters in stem cell therapeutics.

目前基于图像的监测细胞汇合度和状态的分析方法依赖于个人解读,这可能导致细胞疗法的质量差异很大。为了克服这些局限性,我们采集了间充质干细胞在各类培养容器中粘附培养的图像,并使用深度神经网络进行了分析。在各种深度学习方法中,我们选择了一种分类和检测算法来验证细胞的汇合度和状态。我们证实,该图像分类算法对单层和多层图像都有显著的准确性。只有在单层图像中才能检测到异常细胞,因为只有在单层培养中没有异常细胞时才会进行多层培养。这项研究首次基于深度学习方法分析细胞图像,直接影响产量和质量,而产量和质量是干细胞疗法的重要产品参数。
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引用次数: 0
Corrigendum to "In Vivo Stem Cell Imaging Principles and Applications". 体内干细胞成像原理与应用》更正。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-09-10 DOI: 10.15283/23045c
Seongje Hong,Dong-Sung Lee,Geun-Woo Bae,Juhyeong Jeon,Hak Kyun Kim,Siyeon Rhee,Kyung Oh Jung
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引用次数: 0
An Efficient Endothelial Cell Differentiation Protocol Using Bioactive Lipid O-Cyclic Phytosphingosine-1-Phosphate in Human Embryonic Stem Cells. 在人胚胎干细胞中使用生物活性脂质 O-Cyclic Phytosphingosine-1-Phosphate 的高效内皮细胞分化方案。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-09-10 DOI: 10.15283/ijsc24068
Ki-Sang Jo,Won-Jun Jo,Ainsley Mike Antao,Janardhan Keshav Karapurkar,Young Jun Park,Myeong-Jun Choi,Suresh Ramakrishna,Kye-Seong Kim
Bioactive lipids like sphingosine-1-phosphate (S1P) and lysophosphatidic acid have gained significant attention as signaling molecules with regulatory roles in stem cell proliferation and differentiation. The novel chemically synthesized sphingosine metabolite O-cyclic phytosphingosine-1-phosphate (cP1P) is derived from phytosphingosine-1-phosphate (P1P) and shares structural similarities with S1P. Previously, the role of cP1P in regulating ALK3/BMPR signaling during cardiomyocyte differentiation from human embryonic stem cells (hESCs) was demonstrated. In this study, the applicability of cP1P for endothelial cells (ECs) differentiation from hESCs was investigated an efficient method to obtain a high yield of functional ECs over several passages was standardized. The ECs derived from hESCs showed cellular and molecular characteristics similar to the native ECs. Thus, the results of this study open avenues for further research into cP1P-based stem cell differentiation for regenerative therapies.
鞘氨醇-1-磷酸(S1P)和溶血磷脂酸等生物活性脂类作为在干细胞增殖和分化过程中起调控作用的信号分子,受到了广泛关注。化学合成的新型鞘氨醇代谢物 O-环植物鞘氨醇-1-磷酸(cP1P)来源于植物鞘氨醇-1-磷酸(P1P),与 S1P 结构相似。此前,研究证实了 cP1P 在人类胚胎干细胞(hESCs)心肌细胞分化过程中调节 ALK3/BMPR 信号传导的作用。本研究调查了cP1P在从hESCs分化内皮细胞(ECs)过程中的适用性。从 hESCs 中分化出的 ECs 显示出与原生 ECs 相似的细胞和分子特征。因此,这项研究结果为进一步研究基于cP1P的干细胞分化再生疗法开辟了道路。
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引用次数: 0
Human Endometrial Regenerative Cells for Neurological Disorders: Hype or Hope? 人类子宫内膜再生细胞治疗神经系统疾病:炒作还是希望?
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-08-30 Epub Date: 2024-01-08 DOI: 10.15283/ijsc23091
Javad Momeni, Elnaz Naserzadeh, Ali Sepehrinezhad, Rezan Ashayeri Ahmadabad, Sajad Sahab Negah

Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, Alzheimer's disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease's symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.

尽管付出了巨大的努力,但目前还没有发现任何有效的药物能够明显阻止甚至减缓神经系统疾病的发展,如后天性(如脑外伤、脊髓损伤等)和慢性(如帕金森病、阿尔茨海默病等)中枢神经系统疾病。因此,研究人员正在寻找其他治疗方法来控制疾病症状并阻止其恶化。在改变疾病的能力方面,干细胞疗法已成为一个不断扩大的领域。在不同类型的干细胞中,人类子宫内膜再生细胞具有出色的再生特性,适合用于再生医学。它们具有自我更新和分化成三种干细胞的潜力:上皮干细胞、内皮侧群干细胞和间充质干细胞(MSCs)。ERCs可从子宫内膜活检和经血样本中分离出来。然而,关于ERCs对神经系统疾病的影响,目前还没有全面的证据。因此,我们在本分析中首先探讨了这些特定干细胞的特性,然后重点分析了它们在治疗神经系统疾病方面的治疗潜力。
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引用次数: 0
The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review. 间充质干细胞外泌体在脊髓损伤中的作用:系统综述。
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-08-30 Epub Date: 2023-11-29 DOI: 10.15283/ijsc23092
Haoyu Wang, Chunxia Zhao, Qingqing Rong, Jinghe Cao, Hongyi Chen, Ruolin Li, Bin Zhang, Peng Xu

Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.

脊髓损伤(SCI)是一种严重的神经系统疾病,通常导致脊髓的运动、感觉和自主神经功能受损,每年都给家庭和医疗系统带来沉重的负担。由于脊髓损伤的病理生理机制复杂,神经元再生能力差,目前的治疗方案对脊髓功能的恢复效果非常有限。此外,外泌体由于其独特的优势,可以作为货物运输的载体。近年来,一些研究证实用间充质干细胞(mesenchymal stem cells, MSCs)治疗可以促进脊髓损伤神经功能的恢复。MSCs的治疗效果主要与MSCs分泌的外泌体有关,外泌体在SCI治疗中可能具有很大的潜力。本文综述了间充质干细胞衍生外泌体(MSCs-Exos)在SCI治疗中的修复机制,并讨论了基于MSCs-Exos的SCI治疗相关microrna及其作用机制,有助于进一步了解外泌体在SCI中的作用。
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引用次数: 0
Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells. 肿瘤微环境中的谷胱甘肽动态:癌症干细胞和 T 细胞的潜在靶点。
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-08-30 Epub Date: 2024-06-26 DOI: 10.15283/ijsc24060
Youngjun Park, Eui Man Jeong

Glutathione (GSH), the main cellular antioxidant, dynamically influences tumor growth, metastasis, and resistance to therapy in the tumor microenvironment (TME), which comprises cancer cells, immune cells, stromal cells, and non-cellular components, including the extracellular matrix, metabolites, hypoxia, and acidity. Cancer stem cells (CSCs) and T cells are minor but significant cell subsets of the TME. GSH dynamics influences the fate of CSCs and T cells. Here, we explored GSH dynamics in CSCs and T cells within the TME, as well as therapeutic approaches that could target these dynamics.

谷胱甘肽(GSH)是主要的细胞抗氧化剂,它能动态地影响肿瘤微环境(TME)中的肿瘤生长、转移和抗药性,TME 由癌细胞、免疫细胞、基质细胞和非细胞成分(包括细胞外基质、代谢产物、缺氧和酸度)组成。癌症干细胞(CSC)和T细胞是TME中次要但重要的细胞亚群。GSH动态影响着CSCs和T细胞的命运。在这里,我们探讨了癌干细胞和T细胞在TME中的GSH动态,以及针对这些动态的治疗方法。
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引用次数: 0
Establishing Three-Dimensional Explant Culture of Human Dental Pulp Tissue. 建立人类牙髓组织的三维外植体培养。
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-08-30 Epub Date: 2024-07-12 DOI: 10.15283/ijsc23105
Eun Jin Seo, Soyoung Park, Eungyung Lee, Yang Hoon Huh, Ye Eun Ha, Gabor J Tigyi, Taesung Jeong, Il Ho Jang, Jonghyun Shin

Mesenchymal stem cells in the dental tissue indicate a disposition for differentiation into diverse dental lineages and contain enormous potential as the important means for regenerative medicine in dentistry. Among various dental tissues, the dental pulp contains stem cells, progenitor cells and odontoblasts for maintaining dentin homeostasis. The conventional culture of stem cells holds a limit as the living tissue constitutes the three-dimensional (3D) structure. Recent development in the organoid cultures have successfully recapitulated 3D structure and advanced to the assembling of different types. In the current study, the protocol for 3D explant culture of the human dental pulp tissue has been established by adopting the organoid culture. After isolating dental pulp from human tooth, the intact tissue was placed between two layers for Matrigel with addition of the culture medium. The reticular outgrowth of pre-odontoblast layer continued for a month and the random accumulation of dentin was observed near the end. Electron microscopy showed the cellular organization and in situ development of dentin, and immunohistochemistry exhibited the expression of odontoblast and stem cell markers in the outgrowth area. Three-dimensional explant culture of human dental pulp will provide a novel platform for understanding stem cell biology inside the tooth and developing the regenerative medicine.

牙科组织中的间充质干细胞具有分化为不同牙科系的特性,作为牙科再生医学的重要手段,蕴含着巨大的潜力。在各种牙科组织中,牙髓含有维持牙本质平衡的干细胞、祖细胞和牙本质母细胞。由于活组织是三维(3D)结构,传统的干细胞培养方法存在局限性。最近,类器官培养的发展成功地再现了三维结构,并推进了不同类型的组装。本研究采用类器官培养法建立了人类牙髓组织的三维外植体培养方案。从人类牙齿中分离出牙髓后,将完整的牙髓组织置于两层 Matrigel 之间并加入培养基。前牙本质层的网状生长持续了一个月,并在接近末期观察到牙本质的随机堆积。电子显微镜显示了牙本质的细胞组织和原位发育,免疫组化显示了牙本质细胞和干细胞标记物在生长区的表达。人类牙髓的三维外植体培养将为了解牙齿内部的干细胞生物学和开发再生医学提供一个新的平台。
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引用次数: 0
Cytoplasmatic Localization of Six1 in Male Testis and Spermatogonial Stem Cells. 男性睾丸和精原干细胞中 Six1 的细胞质定位
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-08-30 Epub Date: 2024-01-16 DOI: 10.15283/ijsc23093
Mingming Qin, Linzi Ma, Wenjing Du, Dingyao Chen, Guoqun Luo, Zhaoting Liu

Sine oculis homeobox 1 (Six1) is an important factor for embryonic development and carcinoma malignancy. However, the localization of Six1 varies due to protein size and cell types in different organs. In this study, we focus on the expression and localization of Six1 in male reproductive organ via bioinformatics analysis and immunofluorescent detection. The potential interacted proteins with Six1 were also predicted by protein-protein interactions (PPIs) and Enrichr analysis. Bioinformatic data from The Cancer Genome Atlas and Genotype-Tissue Expression project databases showed that SIX1 was highly expressed in normal human testis, but low expressed in the testicular germ cell tumor sample. Human Protein Atlas examination verified that SIX1 level was higher in normal than that in cancer samples. The sub-localization of SIX1 in different reproductive tissues varies but specifically in the cytoplasm and membrane in testicular cells. In mouse cells, single cell RNA-sequencing data analysis indicated that Six1 expression level was higher in mouse spermatogonial stem cells (mSSCs) and differentiating spermatogonial than in other somatic cells. Immunofluorescence staining showed the cytoplasmic localization of Six1 in mouse testis and mSSCs. Further PPIs and Enrichr examination showed the potential interaction of Six1 with bone morphogenetic protein 4 (Bmp4) and catenin Beta-1 (CtnnB1) and stem cell signal pathways. Cytoplasmic localization of Six1 in male testis and mSSCs was probably associated with stem cell related proteins Bmp4 and CtnnB1 for stem cell development.

Sine oculis homeobox 1(Six1)是胚胎发育和癌症恶变的重要因素。然而,由于蛋白质大小和细胞类型的不同,Six1 在不同器官中的定位也不尽相同。本研究通过生物信息学分析和免疫荧光检测,重点研究了Six1在男性生殖器官中的表达和定位。我们还通过蛋白-蛋白相互作用(PPIs)和Enrichr分析预测了与Six1潜在相互作用的蛋白。来自癌症基因组图谱和基因型-组织表达项目数据库的生物信息学数据显示,SIX1在正常人睾丸中高表达,但在睾丸生殖细胞肿瘤样本中低表达。人类蛋白质图谱(Human Protein Atlas)检查证实,正常样本中的 SIX1 水平高于癌症样本。SIX1 在不同生殖组织中的亚定位存在差异,但在睾丸细胞中特别定位于细胞质和细胞膜。在小鼠细胞中,单细胞 RNA 序列数据分析表明,小鼠精原干细胞(mSSCs)和分化精原细胞中的 Six1 表达水平高于其他体细胞。免疫荧光染色显示,在小鼠睾丸和mSSCs中,Six1定位于细胞质。进一步的PPIs和Enrichr检查显示,Six1可能与骨形态发生蛋白4(Bmp4)和Catenin Beta-1(CtnnB1)以及干细胞信号通路相互作用。Six1在雄性睾丸和mSSCs中的细胞质定位可能与干细胞相关蛋白Bmp4和CtnnB1有关,有助于干细胞发育。
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引用次数: 0
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International journal of stem cells
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