International journal of stem cells最新文献

{"title":"<i>In Vitro</i> Generation of Luminal Vasculature in Liver Organoids: From Basic Vascular Biology to Vascularized Hepatic Organoids.","authors":"Hyo Jin Kim,&nbsp;Gyeongmin Kim,&nbsp;Kyun Yoo Chi,&nbsp;Jong-Hoon Kim","doi":"10.15283/ijsc22154","DOIUrl":"https://doi.org/10.15283/ijsc22154","url":null,"abstract":"<p><p>Liver organoids have gained much attention in recent years for their potential applications to liver disease modeling and pharmacologic drug screening. Liver organoids produced <i>in vitro</i> reflect some aspects of the in vivo physiological and pathological conditions of the liver. However, the generation of liver organoids with perfusable luminal vasculature remains a major challenge, hindering precise and effective modeling of liver diseases. Furthermore, vascularization is required for large organoids or assembloids to closely mimic the complexity of tissue architecture without cell death in the core region. A few studies have successfully generated liver organoids with endothelial cell networks, but most of these vascular networks produced luminal structures after being transplanted into tissues of host animals. Therefore, formation of luminal vasculature is an unmet need to overcome the limitation of liver organoids as an <i>in vitro</i> model investigating different acute and chronic liver diseases. Here, we provide an overview of the unique features of hepatic vasculature under pathophysiological conditions and summarize the biochemical and biophysical cues that drive vasculogenesis and angiogenesis <i>in vitro</i>. We also highlight recent progress in generating vascularized liver organoids <i>in vitro</i> and discuss potential strategies that may enable the generation of perfusable luminal vasculature in liver organoids.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/c1/ijsc-16-1-1.PMC9978835.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831203","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":"Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model.","authors":"Han Kyu Chae,&nbsp;Nayoung Suh,&nbsp;Myong Jin Jang,&nbsp;Yu Seon Kim,&nbsp;Bo Hyun Kim,&nbsp;Joomin Aum,&nbsp;Ha Chul Shin,&nbsp;Dalsan You,&nbsp;Bumsik Hong,&nbsp;Hyung Keun Park,&nbsp;Choung-Soo Kim","doi":"10.15283/ijsc21146","DOIUrl":"https://doi.org/10.15283/ijsc21146","url":null,"abstract":"<p><strong>Background and objectives: </strong>We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease.</p><p><strong>Methods and results: </strong>A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10⁶ cells), renal artery moderate dose (RA-MD) (1.0×10⁶ cells), renal artery high dose (RA-HD) (2.0×10⁶ cells), tail vein low dose (TV-LD) (0.5×10⁶ cells), tail vein moderate dose (TV-MD) (1.0×10⁶ cells), and tail vein high dose (TV-HD) (2.0×10⁶ cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups.</p><p><strong>Conclusions: </strong>Our findings confirm the efficacy and safety of high dose (2×10⁶ cells) injection of hBMSC via the tail vein.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"66-77"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/ca/ijsc-16-1-66.PMC9978839.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386447","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":"Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium.","authors":"Soo-Been Jeon,&nbsp;A-Reum Han,&nbsp;Yoo Bin Choi,&nbsp;Ah Reum Lee,&nbsp;Ji Yoon Lee","doi":"10.15283/ijsc22150","DOIUrl":"https://doi.org/10.15283/ijsc22150","url":null,"abstract":"<p><p>γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"108-116"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/3f/ijsc-16-1-108.PMC9978832.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831202","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":"Reduced Cytotoxicity by Repetitive mRNA Transfection in Differentiated Neurons.","authors":"Seung Hwan Ko,&nbsp;Jin Sun Kang,&nbsp;Sang-Mi Kim,&nbsp;Eun-Hye Lee,&nbsp;Chang-Hwan Park","doi":"10.15283/ijsc22125","DOIUrl":"https://doi.org/10.15283/ijsc22125","url":null,"abstract":"<p><strong>Background and objectives: </strong>mRNA-based protein expression technology has been used to express functional proteins. We have previously generated dopamine neurons from rat-embryo derived neural precursor cells (NPCs) through repeated transfection of synthetic transcription factor mRNA encoding dopamine-inducible genes. However, NPCs began to die approximately 10 d post-transfection. In this study, we examined a long-term transfection protocol that did not affect cell viability.</p><p><strong>Methods and results: </strong>Experiments were performed in eight groups sorted according to the start date of mRNA transfection. mRNA was transfected into NPCs daily for 21 d and live cell images of each group were recorded. NPCs which were differentiated for more than five days showed sustained gene expression and appreciable viability despite daily mRNA transfection for 21 d.</p><p><strong>Conclusions: </strong>Repeated mRNA transfection requires cells with a sufficient differentiation period.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"117-122"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/83/ijsc-16-1-117.PMC9978836.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831652","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":"Establishing Rationale for the Clinical Development of Cell Therapy Products: Consensus between Risk and Benefit.","authors":"Seunghoon Han,&nbsp;Hyeon Woo Yim,&nbsp;Hyunsuk Jeong,&nbsp;Suein Choi,&nbsp;Sungpil Han","doi":"10.15283/ijsc21189","DOIUrl":"https://doi.org/10.15283/ijsc21189","url":null,"abstract":"<p><p>Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"16-26"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/ef/ijsc-16-1-16.PMC9978837.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831654","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":"Lupus Heart Disease Modeling with Combination of Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Lupus Patient Serum.","authors":"Narae Park,&nbsp;Yeri Alice Rim,&nbsp;Hyerin Jung,&nbsp;Yoojun Nam,&nbsp;Ji Hyeon Ju","doi":"10.15283/ijsc21158","DOIUrl":"https://doi.org/10.15283/ijsc21158","url":null,"abstract":"<p><strong>Background and objectives: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples.</p><p><strong>Methods and results: </strong>We differentiated CMs from HC- and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs.</p><p><strong>Conclusions: </strong>iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"15 3","pages":"233-246"},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/d0/ijsc-15-3-233.PMC9396017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648600","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":"YBX1 Promotes the Inclusion of RUNX2 Alternative Exon 5 in Dental Pulp Stem Cells.","authors":"Jiaoxiang Shen,&nbsp;Wenting She,&nbsp;Fengxia Zhang,&nbsp;Jihua Guo,&nbsp;Rong Jia","doi":"10.15283/ijsc21035","DOIUrl":"https://doi.org/10.15283/ijsc21035","url":null,"abstract":"<p><strong>Background and objectives: </strong>RUNX2 plays an essential role during the odontoblast differentiation of dental pulp stem cells (DPSCs). RUNX2 Exon 5 is an alternative exon and essential for RUNX2 transcriptional activity. This study aimed to investigate the regulatory mechanisms of RUNX2 exon 5 alternative splicing in human DPSCs.</p><p><strong>Methods and results: </strong>The regulatory motifs of RUNX2 exon 5 were analyzed using the online SpliceAid program. The alternative splicing of RUNX2 exon 5 in DPSCs during mineralization-induced differentiation was analyzed by RT-PCR. To explore the effect of splicing factor YBX1 on exon 5 alternative splicing, gaining or losing function of YBX1 was performed by transfection of YBX1 overexpression plasmid or anti-YBX1 siRNA in DPSCs. Human RUNX2 exon 5 is evolutionarily conserved and alternatively spliced in DPSCs. There are three potential YBX1 binding motifs in RUNX2 exon 5. The inclusion of RUNX2 exon 5 and YBX1 expression level increased significantly during mineralization- induced differentiation in DPSCs. Overexpression of YBX1 significantly increased the inclusion of RUNX2 exon 5 in DPSCs. In contrast, silence of YBX1 significantly reduced the inclusion of exon 5 and the corresponding RUNX2 protein expression level. Knockdown of YBX1 reduced the expression of alkaline phosphatase (ALP) and osteocalcin (OC) and the mineralization ability of DPSCs, while overexpression of YBX1 increased the expression of ALP and OC and the mineralization ability of DPSCs.</p><p><strong>Conclusions: </strong>Human RUNX2 exon 5 is conserved evolutionarily and alternatively spliced in DPSCs. Splicing factor YBX1 promotes the inclusion of RUNX2 exon 5 and improves the mineralization ability of DPSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"15 3","pages":"301-310"},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/98/ijsc-15-3-301.PMC9396021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648595","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":"Xenogeneic Humoral Immune Responses to Human Mesenchymal Stem Cells in Mice.","authors":"Jun-Man Hong,&nbsp;Jin-Hee Kim,&nbsp;Gwang-Hoon Kim,&nbsp;Hyun-Mu Shin,&nbsp;Young-Il Hwang","doi":"10.15283/ijsc21116","DOIUrl":"https://doi.org/10.15283/ijsc21116","url":null,"abstract":"<p><strong>Background and objectives: </strong>Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail.</p><p><strong>Methods and results: </strong>Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton's jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG1 and IgG2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220⁺ GL7⁺) and memory T cells (CD62L⁺ CD44⁺) both in CD4⁺ and CD8⁺ subsets. Similar results were obtained for C57BL/6 mice.</p><p><strong>Conclusions: </strong>hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"15 3","pages":"291-300"},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/36/ijsc-15-3-291.PMC9396016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648596","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":"Diesel Exhaust Particles Impair Therapeutic Effect of Human Wharton's Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis through ROS/ERK/cFos Signaling Pathway.","authors":"Hyun Sung Park,&nbsp;Mi-Kyung Oh,&nbsp;Joong Won Lee,&nbsp;Dong-Hoon Chae,&nbsp;Hansol Joo,&nbsp;Ji Yeon Kang,&nbsp;Hye Bin An,&nbsp;Aaron Yu,&nbsp;Jae Han Park,&nbsp;Hee Min Yoo,&nbsp;Hyun Jun Jung,&nbsp;Uimook Choi,&nbsp;Ji-Won Jung,&nbsp;In-Sook Kim,&nbsp;Il-Hoan Oh,&nbsp;Kyung-Rok Yu","doi":"10.15283/ijsc21178","DOIUrl":"https://doi.org/10.15283/ijsc21178","url":null,"abstract":"<p><strong>Background and objectives: </strong>Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation.</p><p><strong>Methods and results: </strong>Non-apoptotic concentrations of DEP (10 <i>μ</i>g/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including <i>cFos</i>. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 <i>μ</i>g/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS.</p><p><strong>Conclusions: </strong>Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"15 2","pages":"203-216"},"PeriodicalIF":2.3,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/e7/ijsc-15-2-203.PMC9148831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648601","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":"Pharmaceutical Activation of Nrf2 Accelerates Diabetic Wound Healing by Exosomes from Bone Marrow Mesenchymal Stem Cells.","authors":"Lei Wang,&nbsp;Yuhui Cai,&nbsp;Qingrong Zhang,&nbsp;Yi Zhang","doi":"10.15283/ijsc21067","DOIUrl":"https://doi.org/10.15283/ijsc21067","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite advances in wound treatments, chronic diabetic wounds remain a significant medical challenge. Exosomes from mesenchymal stem cells (MSCs) and small molecule activators of nuclear factor erythroid 2-related factor 2 (Nrf2) have emerged as potential therapies for nonhealing diabetic wounds. This study aimed to evaluate the effects of exosomes from bone marrow-derived MSCs (BMSCs) alone, or in combination with a small molecule activator of Nrf2 on diabetic wound healing.</p><p><strong>Methods and results: </strong>BMSCs and endothelial progenitor cells (EPCs) were isolated from the femur and tibia bone marrow of Sprague-Dawley (SD) rats and culture-expanded. Exosomes were harvested from the BMSC culture supernatants through ultracentrifugation. The effects of the exosomes and Nrf2 knockdown, alone or in combination, on EPC tube formation were evaluated. Streptozotocin-induced diabetic rats bearing a fresh full-thickness round wound were treated with the exosomes alone, or in combination with a lentiviral shRNA targeting Nrf2 (Lenti-sh-Nrf2) or tert-butylhydroquinone (tBHQ), a small molecule activator of Nrf2. Two weeks later, wound closure, re-epithelization, collagen deposition, neovascularization, and local inflammation were evaluated. BMSC exosomes promoted while Nrf2 knockdown inhibited EPC tube formation. BMSC exosomes accelerated wound closure, re-epithelization, collagen deposition, and neovascularization, and reduced wound inflammation in diabetic rats. These regenerative and anti-inflammatory effects of the exosomes were inhibited by Lenti-sh-Nrf2 but enhanced by tBHQ administration.</p><p><strong>Conclusions: </strong>BMSC exosomes in combination with a small molecule Nrf2 activator hold promise as a new therapeutic option for chronic diabetic wounds.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"15 2","pages":"164-172"},"PeriodicalIF":2.3,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/94/ijsc-15-2-164.PMC9148840.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39571290","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}