Soo Bin Jang, Yoojung Kim, Han Ceol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho
{"title":"Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes.","authors":"Soo Bin Jang, Yoojung Kim, Han Ceol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho","doi":"10.15283/ijsc24107","DOIUrl":"https://doi.org/10.15283/ijsc24107","url":null,"abstract":"<p><p>Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from <i>Lactobacillus rhamnosus</i>, 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 <i>OCT4</i> and <i>SOX2</i>, 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.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Thermostable bFGF Improves Cell Lifespan by Enhancing Cell Activity in the Long-Term Culture of Human Orbicularis Oculi Stem Cells.","authors":"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","doi":"10.15283/ijsc24039","DOIUrl":"https://doi.org/10.15283/ijsc24039","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myeongjin Song, Kyung Min Lim, Kwonwoo Song, Geun-Ho Kang, Se Jong Kim, Youngseo Lee, Sujin Yu, Ki-Heon Jeong, Ssang-Goo Cho
{"title":"Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-<i>β</i>1-Enriched Small-Sized Extracellular Vesicles.","authors":"Myeongjin Song, Kyung Min Lim, Kwonwoo Song, Geun-Ho Kang, Se Jong Kim, Youngseo Lee, Sujin Yu, Ki-Heon Jeong, Ssang-Goo Cho","doi":"10.15283/ijsc24089","DOIUrl":"https://doi.org/10.15283/ijsc24089","url":null,"abstract":"<p><p>Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton's jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJ-MSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang
{"title":"Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics.","authors":"Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang","doi":"10.15283/ijsc24070","DOIUrl":"https://doi.org/10.15283/ijsc24070","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ki-Sang Jo,Won-Jun Jo,Ainsley Mike Antao,Janardhan Keshav Karapurkar,Young Jun Park,Myeong-Jun Choi,Suresh Ramakrishna,Kye-Seong Kim
{"title":"An Efficient Endothelial Cell Differentiation Protocol Using Bioactive Lipid O-Cyclic Phytosphingosine-1-Phosphate in Human Embryonic Stem Cells.","authors":"Ki-Sang Jo,Won-Jun Jo,Ainsley Mike Antao,Janardhan Keshav Karapurkar,Young Jun Park,Myeong-Jun Choi,Suresh Ramakrishna,Kye-Seong Kim","doi":"10.15283/ijsc24068","DOIUrl":"https://doi.org/10.15283/ijsc24068","url":null,"abstract":"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.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"23 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Woo Kim, Kyu Sik Jeong, Jin Kim, Seul-Gi Lee, C-Yoon Kim, Hyung Min Chung
{"title":"Generation of an Isogenic Hereditary Hemorrhagic Telangiectasia Model via Prime Editing in Human Induced Pluripotent Stem Cells.","authors":"Min Woo Kim, Kyu Sik Jeong, Jin Kim, Seul-Gi Lee, C-Yoon Kim, Hyung Min Chung","doi":"10.15283/ijsc24084","DOIUrl":"https://doi.org/10.15283/ijsc24084","url":null,"abstract":"<p><p>Prime editing (PE) is a recently developed genome-editing technique that enables versatile editing. Despite its flexibility and potential, applying PE in human induced pluripotent stem cells (hiPSCs) has not been extensively addressed. Genetic disease models using patient-derived hiPSCs have been used to study mechanisms and drug efficacy. However, genetic differences between patient and control cells have been attributed to the inaccuracy of the disease model, highlighting the significance of isogenic hiPSC models. Hereditary hemorrhagic telangiectasia 1 (HHT1) is a genetic disorder caused by an autosomal dominant mutation in endoglin (<i>ENG</i>). Although previous HHT models using mice and HUVEC have been used, these models did not sufficiently elucidate the relationship between the genotype and disease phenotype in HHT, demanding more clinically relevant models that reflect human genetics. Therefore, in this study, we used PE to propose a method for establishing an isogenic hiPSC line. Clinically reported target mutation in <i>ENG</i> was selected, and a strategy for PE was designed. After cloning the <i>ENG</i>ineered PE guide RNA, hiPSCs were nucleofected along with PEmax and hMLH1dn plasmids. As a result, hiPSC clones with the intended mutation were obtained, which showed no changes in pluripotency or genetic integrity. Furthermore, introducing the <i>ENG</i> mutation increased the expression of proangiogenic markers during endothelial organoid differentiation. Consequently, our results suggest the potential of PE as a toolkit for establishing isogenic lines, enabling disease modeling based on hiPSC-derived disease-related cells or organoids. This approach is expected to stimulate mechanistic and therapeutic studies on genetic diseases.a.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human Endometrial Regenerative Cells for Neurological Disorders: Hype or Hope?","authors":"Javad Momeni, Elnaz Naserzadeh, Ali Sepehrinezhad, Rezan Ashayeri Ahmadabad, Sajad Sahab Negah","doi":"10.15283/ijsc23091","DOIUrl":"10.15283/ijsc23091","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"224-235"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review.","authors":"Haoyu Wang, Chunxia Zhao, Qingqing Rong, Jinghe Cao, Hongyi Chen, Ruolin Li, Bin Zhang, Peng Xu","doi":"10.15283/ijsc23092","DOIUrl":"10.15283/ijsc23092","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"236-252"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.","authors":"Youngjun Park, Eui Man Jeong","doi":"10.15283/ijsc24060","DOIUrl":"10.15283/ijsc24060","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"270-283"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}