Regenerative Therapy最新文献

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Exploring SSEA3 as an emerging biomarker for assessing the regenerative potential of dental pulp-derived stem cells 探索将 SSEA3 作为评估牙髓干细胞再生潜力的新兴生物标志物
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-25 DOI: 10.1016/j.reth.2024.05.004
Jumpei Shirakawa , Edward H. Ntege , Masuo Takemura , Sho Miyamoto , Toshihiro Kawano , Chisato Sampei , Hayato Kawabata , Hiroyuki Nakamura , Hiroshi Sunami , Tadayoshi Hayata , Yusuke Shimizu
{"title":"Exploring SSEA3 as an emerging biomarker for assessing the regenerative potential of dental pulp-derived stem cells","authors":"Jumpei Shirakawa ,&nbsp;Edward H. Ntege ,&nbsp;Masuo Takemura ,&nbsp;Sho Miyamoto ,&nbsp;Toshihiro Kawano ,&nbsp;Chisato Sampei ,&nbsp;Hayato Kawabata ,&nbsp;Hiroyuki Nakamura ,&nbsp;Hiroshi Sunami ,&nbsp;Tadayoshi Hayata ,&nbsp;Yusuke Shimizu","doi":"10.1016/j.reth.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.004","url":null,"abstract":"<div><h3>Background</h3><p>Human dental pulp-derived stem cells (hDPSCs) have emerged as a promising source for adult stem cell-based regenerative medicine. Stage-specific embryonic antigen 3 (SSEA3) is a cell surface marker associated with Multilineage-differentiating stress-enduring (Muse) cells, a subpopulation of human bone marrow-derived stem cells (hBMSCs), known for their potent regenerative potential and safety profile. In this study, we investigated the influence of the prolonged culture period and the number of culture passages on the regenerative capacity of hDPSCs and explored the association between SSEA3 expression and their regenerative abilities.</p></div><div><h3>Methods</h3><p>hDPSCs were isolated and cultured for up to 20 passages. Cell proliferation, migration, and osteogenic, adipogenic and neurogenic differentiation potential were assessed at passages 5, 10, and 20. Flow cytometry and immunofluorescence were employed to analyze SSEA3 expression. RNA sequencing (RNA-seq) was performed on SSEA3-positive and SSEA3-negative hDPSCs to identify differentially expressed genes and associated pathways.</p></div><div><h3>Results</h3><p>Our findings demonstrated a progressive decline in hDPSCs proliferation and migration capacity with increasing passage number. Conversely, cell size exhibited a positive correlation with passage number. Early passage hDPSCs displayed superior osteogenic and adipogenic differentiation potential. Notably, SSEA3 expression exhibited a significant negative correlation with passage numbers, reflecting the observed decline in differentiation capacity. RNA-seq analysis revealed distinct transcriptional profiles between SSEA3-positive and SSEA3-negative hDPSCs. SSEA3-positive cells displayed upregulation of genes associated with ectodermal differentiation and downregulation of genes involved in cell adhesion.</p></div><div><h3>Conclusions</h3><p>This study elucidates the impact of passaging on hDPSC behavior and suggests SSEA3 as a valuable biomarker for evaluating stemness and regenerative potential. SSEA3-positive hDPSCs, functionally analogous to Muse cells, represent a promising cell population for developing targeted regenerative therapies with potentially improved clinical outcomes.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000841/pdfft?md5=f72a12919d3b83627040842485d671fb&pid=1-s2.0-S2352320424000841-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141095770","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
CircRNA SEC24A promotes osteoarthritis through miR-107-5p/CASP3 axis CircRNA SEC24A通过miR-107-5p/CASP3轴促进骨关节炎的发生
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-24 DOI: 10.1016/j.reth.2024.04.011
Tuerxunjiang Dadihanc , Yong Zhang , Guo-Qing Li , Hai-Kang Zhou , Jingyong Huang , Xue Zhang , Zhi-Qiang Li , Hai-Rong Ma
{"title":"CircRNA SEC24A promotes osteoarthritis through miR-107-5p/CASP3 axis","authors":"Tuerxunjiang Dadihanc ,&nbsp;Yong Zhang ,&nbsp;Guo-Qing Li ,&nbsp;Hai-Kang Zhou ,&nbsp;Jingyong Huang ,&nbsp;Xue Zhang ,&nbsp;Zhi-Qiang Li ,&nbsp;Hai-Rong Ma","doi":"10.1016/j.reth.2024.04.011","DOIUrl":"https://doi.org/10.1016/j.reth.2024.04.011","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) is the most frequently diagnosed chronic joint disease. CircSEC24A is significantly elevated in OA chondrocytes upon IL-1β stimulation. However, its biological function in OA is still not fully understood.</p></div><div><h3>Methods</h3><p>The circRNAs-miRNA-mRNA network was predicted by bioinformatics analysis. An <em>in vitro</em> OA chondrocytes model was established by IL-1β stimulation. The expression of circSEC24A, miR-107-5p, CASP3, apoptosis-related molecules and extracellular matrix (ECM) components were detected by Western blot and qRT-PCR. MTT assay and Annexin V/PI staining were employed to monitor cell viability and apoptosis, respectively. The interaction between circSEC24A and miR-107-5p, as well as the binding between miR-107-5p and CASP3 3’ UTR were detected by luciferase reporter and RIP assays. Cytokine secretion was monitored by ELISA assay. The role of circSEC24A was also explored in anterior cruciate ligament transection (ACLT) rat models.</p></div><div><h3>Results</h3><p>CircSEC24A and CASP3 were increased, but miR-107-5p was decreased in rat OA cartilage tissues and OA chondrocytes. CircSEC24A acted as a sponge of miR-107-5p. Knockdown of circSEC24A promoted chondrocyte proliferation, but suppressed chondrocyte apoptosis, ECM degradation and inflammation via sponging miR-107-5p. CASP3 was identified as a miR-107-5p target gene. MiR-107-5p mimics protected against OA progression via targeting CASP3. Silencing of circSEC24A alleviated OA progression in ACLT model.</p></div><div><h3>Conclusion</h3><p>CircSEC24A promotes OA progression through miR-107-5p/CASP3 axis.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000737/pdfft?md5=84117dc326a84491f255a86b6ca2f8c4&pid=1-s2.0-S2352320424000737-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089952","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
Therapeutic potential of dedifferentiated fat cells in a rat model of osteoarthritis of the knee 再分化脂肪细胞在膝骨关节炎大鼠模型中的治疗潜力
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-22 DOI: 10.1016/j.reth.2024.05.006
Noriyuki Endo , Taro Matsumoto , Tomohiko Kazama , Koichiro Kano , Manabu Shimizu , Keinosuke Ryu , Yasuaki Tokuhashi , Kazuyoshi Nakanishi
{"title":"Therapeutic potential of dedifferentiated fat cells in a rat model of osteoarthritis of the knee","authors":"Noriyuki Endo ,&nbsp;Taro Matsumoto ,&nbsp;Tomohiko Kazama ,&nbsp;Koichiro Kano ,&nbsp;Manabu Shimizu ,&nbsp;Keinosuke Ryu ,&nbsp;Yasuaki Tokuhashi ,&nbsp;Kazuyoshi Nakanishi","doi":"10.1016/j.reth.2024.05.006","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.006","url":null,"abstract":"<div><h3>Introduction</h3><p>Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin.</p></div><div><h3>Methods</h3><p>In the cell transplantation experiment, rats were assigned to the DFAT and Control group (n = 10 in each group) and underwent anterior cruciate ligament transection (ACLT) accompanied by medial meniscus resection (MMx) to induce OA. One week later, they received intra-articular injections of 1 × 10<sup>6</sup> DFATs (DFAT group) or PBS (control group) four times, with a weekly administration frequency. Macroscopic and microscopic evaluations were conducted five weeks post-surgery. In the in vitro experiments. DFATs derived from the IFP (IFP-DFATs) and SC (SC-DFATs) were prepared from donor-matched tissue samples (n = 3). The gene expression of <em>PTGS2</em>, <em>TNFAIP6, PRG4, BMP2,</em> and <em>BMP6</em> under TNF-α or IFN-γ stimulation in these cells was evaluated using RT-PCR. Furthermore, the effect of co-culturing synovial fibroblasts with DFATs on the gene expression of <em>ADAMTS4</em> and <em>IL-6</em> were evaluated.</p></div><div><h3>Results</h3><p>Intra-articular injections of DFATs significantly inhibited cartilage degeneration in the rat OA model induced by ACLT and MMx. RT-PCR analysis revealed that both IFP-DFATs and SC-DFATs upregulated the expression of genes involved in immune regulation, anti-inflammation, and cartilage protection such as <em>PTGS2</em>, <em>TNFAIP6</em>, and <em>BMP2</em>, under stimulation by inflammatory cytokines. Co-culture with DFATs suppressed the expression of <em>ADAMTS4</em> and <em>IL6</em> in synovial fibroblasts.</p></div><div><h3>Conclusions</h3><p>The intra-articular injection of DFATs resulted in chondroprotective effects in the rat OA model. Both SC-DFATs and IFP-DFATs induced the expression of anti-inflammatory and chondroprotective genes in vitro. These results indicate that DFATs appear to possess therapeutic potential in inhibiting cartilage degradation and could serve as a promising cellular resource for OA treatment.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000865/pdfft?md5=ac0610c17374d77e6e6f76d21f1b64a8&pid=1-s2.0-S2352320424000865-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083494","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
METTL3 promotes the osteogenic differentiation of periosteum-derived MSCs via regulation of the HOXD8/ITGA5 axis in congenital pseudarthrosis METTL3通过调控HOXD8/ITGA5轴促进先天性假关节中骨膜来源间充质干细胞的成骨分化
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-21 DOI: 10.1016/j.reth.2024.04.004
Weihua Ye, Zheng Liu, Yaoxi Liu, Han Xiao, Qian Tan, An Yan, Guanghui Zhu
{"title":"METTL3 promotes the osteogenic differentiation of periosteum-derived MSCs via regulation of the HOXD8/ITGA5 axis in congenital pseudarthrosis","authors":"Weihua Ye,&nbsp;Zheng Liu,&nbsp;Yaoxi Liu,&nbsp;Han Xiao,&nbsp;Qian Tan,&nbsp;An Yan,&nbsp;Guanghui Zhu","doi":"10.1016/j.reth.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.reth.2024.04.004","url":null,"abstract":"<div><h3>Background</h3><p>Congenital pseudarthrosis of the tibia (CPT) is a dominant health challenge in pediatric orthopedics. The essential process in the development of CPT is the limited capacity of mesenchymal stem cells (MSCs) derived from CPT to undergo osteogenic differentiation. Our research aimed to elucidate the role and mechanism of methyltransferase-like 3 (METTL3) in the osteogenic differentiation process of CPT MSCs.</p></div><div><h3>Methods</h3><p>The osteogenic differentiation medium was used to culture MSCs, and the detection of osteogenic differentiation was performed using Alizarin Red S and alkaline phosphatase (ALP) assays. Gene or protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, or immunofluorescence (IF) staining. The m<sup>6</sup>A modification of Homeobox D8 (HOXD8) was verified by methylated RNA immunoprecipitation (MeRIP) assay. Interactions between METTL3 and HOXD8 or HOXD8 and integrin alpha 5 (ITGA5) promoter were validated by the luciferase reporter gene, RIP, and chromatin immunoprecipitation (ChIP) assays.</p></div><div><h3>Results</h3><p>METTL3 overexpression enhanced CPT MSCs' osteogenic differentiation. METTL3 stabilized the HOXD8 in an m<sup>6</sup>A-dependent manner. Moreover, the overexpressed ITGA5 up-regulated the CPT MSCs’ osteogenic differentiation. Further, HOXD8 could transcriptionally activate ITGA5. METTL3 increased the transcription of ITGA5 via HOXD8 to enhance the osteogenic differentiation of CPT MSCs.</p></div><div><h3>Conclusion</h3><p>METTL3 promoted osteogenic differentiation via modulating the HOXD8/ITGA5 axis in CPT MSCs.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400066X/pdfft?md5=67d2ffb950655a520e6b51b3c2181f29&pid=1-s2.0-S235232042400066X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073123","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
PPARA ameliorates sepsis-induced myocardial injury via promoting macrophage M2 polarization by interacting with DUSP1 PPARA 通过与 DUSP1 相互作用促进巨噬细胞 M2 极化,从而改善败血症诱发的心肌损伤
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-18 DOI: 10.1016/j.reth.2024.04.017
Li Cheng , Dezhi Liu , Shanglan Gao
{"title":"PPARA ameliorates sepsis-induced myocardial injury via promoting macrophage M2 polarization by interacting with DUSP1","authors":"Li Cheng ,&nbsp;Dezhi Liu ,&nbsp;Shanglan Gao","doi":"10.1016/j.reth.2024.04.017","DOIUrl":"https://doi.org/10.1016/j.reth.2024.04.017","url":null,"abstract":"<div><h3>Background</h3><p>The morbidity and mortality of sepsis are increasing year by year. Statistically, 40–50% of patients with sepsis have concomitant myocardial injury, and its mortality rate is higher than that of patients with sepsis only. Therefore, it is of great significance to elucidate the mechanism of sepsis-induced myocardial injury.</p></div><div><h3>Methods and results</h3><p>Human monocytes (THP-1) were used to induce M0 macrophages, followed by treated with lipopolysaccharide (LPS). Cardiomyocytes (AC16) were co-cultured with the conditioned medium of LPS-induced macrophages to induce injury. Quantitative real-time PCR was employed to detect the mRNA levels of peroxisome proliferator-activated receptor α (PPARA) and dual specificity phosphatase 1 (DUSP1). Protein levels of PPARA, macrophage polarization-related markers, apoptosis-related markers, mitochondria-related proteins, and DUSP1 were analyzed by Western blot. Flow cytometry was used to assess M1/M2 cell rates and apoptosis. Low PPARA expression could serve as a biomarker for patients with sepsis. PPARA overexpression enhanced M2 polarization and suppressed M1 polarization in LPS-induced macrophages, and it could alleviate cardiomyocyte injury in co-cultured system. PPARA bound to the DUSP1 promoter region and facilitated its expression. DUSP1 knockdown reversed the effect of PPARA overexpression on M2 polarization and cardiomyocyte injury.</p></div><div><h3>Conclusion</h3><p>PPARA attenuated cardiomyocyte injury by promoting macrophage M2 polarization through increasing DUSP1 expression, suggesting that PPARA might be a therapy target for sepsis-induced myocardial injury.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000798/pdfft?md5=3622d6db14d00dc2e9df5d781249db9c&pid=1-s2.0-S2352320424000798-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141068402","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
Investigating the attenuating effects of metformin-loaded selenium nanoparticles coupled with Myrtus communis L. flower extract on CaOx deposition in male Sprague Dawley rat kidneys via regulating MAPK signaling pathway 研究二甲双胍载硒纳米颗粒与桃金娘花提取物通过调节 MAPK 信号通路对雄性 Sprague Dawley 大鼠肾脏氧化钙沉积的抑制作用
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-17 DOI: 10.1016/j.reth.2024.04.006
Jian Kang , Yanqing Tong
{"title":"Investigating the attenuating effects of metformin-loaded selenium nanoparticles coupled with Myrtus communis L. flower extract on CaOx deposition in male Sprague Dawley rat kidneys via regulating MAPK signaling pathway","authors":"Jian Kang ,&nbsp;Yanqing Tong","doi":"10.1016/j.reth.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.reth.2024.04.006","url":null,"abstract":"<div><p>Kidney stones are a foremost clinical concern in urology with CaOx crystals accounting for roughly 80% of these renal formations. This research endeavor seeks to ascertain the protective effects of Metformin-encapsulated selenium nanoparticles (M@Se NPs), combined with a 55% hydroethanolic flower extract from <em>Myrtus communis L.</em> (<em>MCL</em>) in countering the formation of kidney stones in Male Sprague Dawley rats. The particle's diameter was measured to be 39 nm and 13.8 nm from DLS and HR-TEM analysis. Rat groups administered with the <em>MCL</em>-M@Se NPs (1:1.5:1) exhibited reduced renal stone formation in urine and serum analysis compared to the negative control group. Histological evaluations of kidney samples using H&amp;E, and MTS staining indicated a subdued presence of ECM deposition in contrast to other rat groups. Conclusively, the protective mechanism of <em>MCL</em>-M@Se NPs against CaOx stone damage can be confidently attributed to the obstruction of the MAPK signaling pathway.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000683/pdfft?md5=968556b574c56a3eeb656365573cc447&pid=1-s2.0-S2352320424000683-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140952166","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
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) activates p38 to affect pulmonary fibrosis 肝素结合表皮生长因子样生长因子(HB-EGF)激活 p38 影响肺纤维化
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-17 DOI: 10.1016/j.reth.2024.05.002
Yan An , Su-Yan Yan , Wei Xu , Mei-Qi Li , Rong-Rong Dong , Qing-Rui Yang , Zhen-Zhen Ma
{"title":"Heparin-binding epidermal growth factor-like growth factor (HB-EGF) activates p38 to affect pulmonary fibrosis","authors":"Yan An ,&nbsp;Su-Yan Yan ,&nbsp;Wei Xu ,&nbsp;Mei-Qi Li ,&nbsp;Rong-Rong Dong ,&nbsp;Qing-Rui Yang ,&nbsp;Zhen-Zhen Ma","doi":"10.1016/j.reth.2024.05.002","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.002","url":null,"abstract":"<div><h3>Objective</h3><p>We aimed to examine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) affects the lung fibrosis process through the activation of p38 protein in mitogen-activated protein kinases (MAPK) signaling pathway, as well as the expression of downstream inflammatory factors.</p></div><div><h3>Methods</h3><p>The expression levels of HB-EGF, collagen type I (COL-I), and hexokinase 2 (HK2) in peripheral blood mononuclear cells (PBMCs) of patients with connective tissue disease-related interstitial lung disease (CTD-ILD) were examined by qPCR, Western blotting and ELISA.</p></div><div><h3>Results</h3><p>In vitro experiments showed that HB-EGF was increased in almost all subtypes [rheumatoid arthritis (RA), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIMs)] as well as in all groups (P &lt; 0.05). For embryonic lung fibroblast (A549) cells, the expression levels of HK2 and α-smooth muscle actin (α-SMA) genes were elevated during 0–4 h and then plateaued. Transforming growth factor-β1 (TGF-β1) induced fibrosis in human embryonic lung fibroblasts (MRC-5) cells and A549 for a certain period of time, but the degree of induction varied, which may be related to the redifferentiability of cells at different spatial locations. Moreover, HB-EGF at concentrations above 1 ng/ml stimulation increased COL-I expression (P &lt; 0.05), and for α-SMA gene, even 1 ng/ml concentration of HB-EGF had a stimulatory effect, and different concentrations of HB-EGF did activate the expression of p38 in a concentration-dependent manner within a certain concentration range, and by The qPCR results showed that for interleukin 6 (IL-6), an inflammatory factor regulated downstream of p38, the expression was significantly increased in A549 cells compared to control (P &lt; 0.05), but tumor necrosis factor-α (TNF-α) expression was downregulated (P &lt; 0.05), but for interleukin-1β (IL-1β) gene, there was no significant difference in A549 cells, and expression was downregulated in MRC-5 cells. Therefore, it is suggested that HB-EGF regulates the expression of inflammatory factors through p38 will be differential across cells.</p></div><div><h3>Conclusion</h3><p>Our study shows that HB-EGF can suppress pulmonary fibrosis through downstream activation of p38/MAPK pathway activity, as well as the expression of various inflammatory factors downstream of it.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000828/pdfft?md5=973d9a137d82de2693d173eb26a959a3&pid=1-s2.0-S2352320424000828-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140952169","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
Opinions on research involving human embryo models by researchers and the general public 研究人员和公众对涉及人类胚胎模型研究的意见
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-15 DOI: 10.1016/j.reth.2024.05.001
Hideki Yui , Yoshimi Yashiro , Kaori Muto , Saori Watanabe , Yukitaka Kiya , Yusuke Inoue , Zentaro Yamagata
{"title":"Opinions on research involving human embryo models by researchers and the general public","authors":"Hideki Yui ,&nbsp;Yoshimi Yashiro ,&nbsp;Kaori Muto ,&nbsp;Saori Watanabe ,&nbsp;Yukitaka Kiya ,&nbsp;Yusuke Inoue ,&nbsp;Zentaro Yamagata","doi":"10.1016/j.reth.2024.05.001","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.001","url":null,"abstract":"<div><p>Rules and ethical considerations regarding research on embryo models have been debated across numerous countries. In this paper, we provide insights from our attitude survey conducted among Japanese researchers, including members of the Japanese Society for Regenerative Medicine, and among the general public residing in Japan, the US, the UK, Canada, and Australia. Our survey revealed that many researchers expressed the need for clear guidelines for embryo model research. Furthermore, a minority but significant portion of the general public in each country expressed opposition to research on embryo models but did not oppose research involving real embryos.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000816/pdfft?md5=64b4d49d829b7b8c645e7f0f632242c1&pid=1-s2.0-S2352320424000816-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140948422","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 impact of acute and chronic aerobic and resistance exercise on stem cell mobilization: A review of effects in healthy and diseased individuals across different age groups 急性和慢性有氧运动及阻力运动对干细胞动员的影响:对不同年龄组健康和患病人群的影响综述
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-07 DOI: 10.1016/j.reth.2024.04.013
Wei Li , Lingzhen Chen , S. Mohammad Sajadi , Sh. Baghaei , Soheil Salahshour
{"title":"The impact of acute and chronic aerobic and resistance exercise on stem cell mobilization: A review of effects in healthy and diseased individuals across different age groups","authors":"Wei Li ,&nbsp;Lingzhen Chen ,&nbsp;S. Mohammad Sajadi ,&nbsp;Sh. Baghaei ,&nbsp;Soheil Salahshour","doi":"10.1016/j.reth.2024.04.013","DOIUrl":"https://doi.org/10.1016/j.reth.2024.04.013","url":null,"abstract":"<div><p>Stem cells (SCs) play a crucial role in tissue repair, regeneration, and maintaining physiological homeostasis. Exercise mobilizes and enhances the function of SCs. This review examines the effects of acute and chronic aerobic and resistance exercise on the population of SCs in healthy and diseased individuals across different age groups. Both acute intense exercise and moderate regular training increase circulating precursor cells CD34<sup>+</sup> and, in particular, the subset of angiogenic progenitor cells (APCs) CD34+/KDR+. Conversely, chronic exercise training has conflicting effects on circulating CD34<sup>+</sup> cells and their function, which are likely influenced by exercise dosage, the health status of the participants, and the methodologies employed. While acute activity promotes transient mobilization, regular exercise often leads to an increased number of progenitors and more sustainable functionality. Short interventions lasting 10–21 days mobilize CD34+/KDR + APCs in sedentary elderly individuals, indicating the inherent capacity of the body to rapidly activate tissue-reparative SCs during activity. However, further investigation is needed to determine the optimal exercise regimens for enhancing SC mobilization, elucidating the underlying mechanisms, and establishing functional benefits for health and disease prevention. Current evidence supports the integration of intense exercise with chronic training in exercise protocols aimed at activating the inherent regenerative potential through SC mobilization. The physical activity promotes endogenous repair processes, and research on exercise protocols that effectively mobilize SCs can provide innovative guidelines designed for lifelong tissue regeneration. An artificial neural network (ANN) was developed to estimate the effects of modifying elderly individuals and implementing chronic resistance exercise on stem cell mobilization and its impact on individuals and exercise. The network's predictions were validated using linear regression and found to be acceptable compared to experimental results.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000750/pdfft?md5=c329aa0b1eac5c603a8196e5c523bc93&pid=1-s2.0-S2352320424000750-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880089","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
Enriched human embryonic stem cells-derived CD133+, CD24+ renal progenitors engraft and restore function in a gentamicin-induced kidney injury in mice 富集人类胚胎干细胞衍生的 CD133+、CD24+ 肾祖细胞在庆大霉素诱导的小鼠肾损伤中进行移植并恢复功能
IF 4.3 3区 环境科学与生态学
Regenerative Therapy Pub Date : 2024-05-07 DOI: 10.1016/j.reth.2024.04.015
Maryam Bahrami , Hojjat Allah Abbaszadeh , Mohsen Norouzian , Mohammad-Amin Abdollahifar , Navid Ahmady Roozbahany , Maryam Saber , Masoumeh Azimi , Ehsan Ehsani , Mohsen Bakhtiyari , Andreas L. Serra , Reza Moghadasali
{"title":"Enriched human embryonic stem cells-derived CD133+, CD24+ renal progenitors engraft and restore function in a gentamicin-induced kidney injury in mice","authors":"Maryam Bahrami ,&nbsp;Hojjat Allah Abbaszadeh ,&nbsp;Mohsen Norouzian ,&nbsp;Mohammad-Amin Abdollahifar ,&nbsp;Navid Ahmady Roozbahany ,&nbsp;Maryam Saber ,&nbsp;Masoumeh Azimi ,&nbsp;Ehsan Ehsani ,&nbsp;Mohsen Bakhtiyari ,&nbsp;Andreas L. Serra ,&nbsp;Reza Moghadasali","doi":"10.1016/j.reth.2024.04.015","DOIUrl":"https://doi.org/10.1016/j.reth.2024.04.015","url":null,"abstract":"<div><h3>Introduction</h3><p>Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI.</p></div><div><h3>Methods</h3><p>Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24<sup>+</sup> renal progenitor cells and evaluate their functional activity in alleviating AKI.</p></div><div><h3>Results</h3><p>The obtained results show that hESCs-derived CD133+CD24<sup>+</sup> RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis.</p></div><div><h3>Conclusion</h3><p>The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000774/pdfft?md5=1769658d50f13db4c8fcc9fc91bac27d&pid=1-s2.0-S2352320424000774-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880090","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
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