Human Cell最新文献_第5页

Long non-coding RNA SIX1-1 promotes proliferation of cervical cancer cells via negative transcriptional regulation of RASD1. 长非编码 RNA SIX1-1 通过对 RASD1 的负转录调控促进宫颈癌细胞的增殖。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1007/s13577-024-01104-8

Xiaoli Hu, Wan Wang, Teng Ma, Wanqi Zhang, Xiaohui Tang, Yingru Zheng, Xiuhui Zheng

{"title":"Long non-coding RNA SIX1-1 promotes proliferation of cervical cancer cells via negative transcriptional regulation of RASD1.","authors":"Xiaoli Hu, Wan Wang, Teng Ma, Wanqi Zhang, Xiaohui Tang, Yingru Zheng, Xiuhui Zheng","doi":"10.1007/s13577-024-01104-8","DOIUrl":"10.1007/s13577-024-01104-8","url":null,"abstract":"Cervical cancer poses a significant health burden for women globally, and the rapid proliferation of cervical cancer cells greatly worsens patient prognosis. Long non-coding RNAs (lncRNAs) play a crucial role in regulating tumor cell proliferation. However, the involvement of lncRNAs in cervical cancer cell proliferation remains unclear. In this study, we investigated the lncRNA SIX1-1, which was found to be upregulated in cervical cancer tissues and cell lines. Functional assays revealed that knockdown of SIX1-1 inhibited cell proliferation in vitro and reduced tumor growth in vivo. Mechanistically, SIX1-1 was predominantly localized in the nucleus and could bind with DNMT1 protein. The expression of SIX1-1 enhanced the interaction of DNMT1 with RASD1 promoter, leading to the methylation of the promoter and decreased mRNA transcription. Then RASD1 downregulation activated the cAMP/PKA/CREB signaling pathway, promoting cell proliferation. Rescue experiments showed that knockdown of RASD1 restored the inhibited cell proliferation caused by decreased expression of SIX1-1, indicating that RASD1 acted as the functional mediator of SIX1-1. In conclusion, SIX1-1 promoted cervical cancer cell proliferation by modulating RASD1 expression. This suggests that targeting the SIX1-1/RASD1 axis could be a potential antitumor strategy for cervical cancer.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141628145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of 3D-iNET ORION: a novel, pre-clinical, three-dimensional in vitro cell model for modeling human metastatic neuroendocrine tumor of the pancreas. 开发 3D-iNET ORION：用于模拟人类胰腺转移性神经内分泌肿瘤的新型临床前三维体外细胞模型。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1007/s13577-024-01113-7

Jan Strnadel, Mark A Valasek, Grace Y Lin, Huahui Lin, Ann M Ponsford Tipps, Sang Myung Woo, Ken Fujimura, Huawei Wang, Sunkyu Choi, Jack Bui, Christopher Hermosillo, Kristen Jepsen, Michael R Navarro, Jonathan A Kelber, Richard L Klemke, Michael Bouvet

{"title":"Development of 3D-iNET ORION: a novel, pre-clinical, three-dimensional in vitro cell model for modeling human metastatic neuroendocrine tumor of the pancreas.","authors":"Jan Strnadel, Mark A Valasek, Grace Y Lin, Huahui Lin, Ann M Ponsford Tipps, Sang Myung Woo, Ken Fujimura, Huawei Wang, Sunkyu Choi, Jack Bui, Christopher Hermosillo, Kristen Jepsen, Michael R Navarro, Jonathan A Kelber, Richard L Klemke, Michael Bouvet","doi":"10.1007/s13577-024-01113-7","DOIUrl":"10.1007/s13577-024-01113-7","url":null,"abstract":"Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular signal-regulated kinase is activated in podocytes from patients with diabetic nephropathy. 糖尿病肾病患者荚膜细胞中的细胞外信号调节激酶被激活。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-07-25 DOI: 10.1007/s13577-024-01108-4

Aoi Yamashiro, Yasushi Satoh, Shogo Endo, Naoki Oshima

{"title":"Extracellular signal-regulated kinase is activated in podocytes from patients with diabetic nephropathy.","authors":"Aoi Yamashiro, Yasushi Satoh, Shogo Endo, Naoki Oshima","doi":"10.1007/s13577-024-01108-4","DOIUrl":"10.1007/s13577-024-01108-4","url":null,"abstract":"In the past few decades, the global prevalence of diabetes has provided us with a warning about future chronic complications. Diabetic nephropathy (DN) is the main cause of end-stage kidney disease. Podocytes in the glomerulus play a critical role in regulating glomerular permeability, and podocyte injury is one of the main causes of DN. Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family that plays critical roles in intracellular signal transduction. In human patients with DN, phosphorylated ERK (pERK), the active form of ERK, is increased in the glomeruli. However, information on the expression of pERK, specifically in podocytes in DN, is limited. Meanwhile, high glucose induces ERK activation in immortalized podocyte cell lines, suggesting the involvement of podocytic ERK in DN. We performed an immunohistochemical study using Wilms' tumor-1 (WT-1) as a podocyte-specific marker to investigate whether podocytic pERK levels are increased in patients with DN. In the glomeruli of the DN group, we observed remarkable co-staining for WT-1 and pERK. In contrast, the glomeruli of the control group contained only a few pERK-positive podocytes. Statistical analyses revealed that, relative to healthy controls, patients with DN showed significantly increased pERK expression levels in cells that were positive for WT-1 (DN: 51.3 ± 13.1% vs. control: 7.3 ± 1.6%, p = 0.0158, t-test, n = 4 for each group). This suggests that ERK activation in podocytes is involved in the pathogenesis of DN.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor. 比较来自同一无功能胰腺神经内分泌肿瘤患者的不同临床前模型。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI: 10.1007/s13577-024-01107-5

Yan Wang, Zeng Ye, Xin Lou, Junfeng Xu, Desheng Jing, Chenjie Zhou, Yi Qin, Jie Chen, Xiaowu Xu, Xianjun Yu, Shunrong Ji

{"title":"Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor.","authors":"Yan Wang, Zeng Ye, Xin Lou, Junfeng Xu, Desheng Jing, Chenjie Zhou, Yi Qin, Jie Chen, Xiaowu Xu, Xianjun Yu, Shunrong Ji","doi":"10.1007/s13577-024-01107-5","DOIUrl":"10.1007/s13577-024-01107-5","url":null,"abstract":"Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EP300 promotes tumor stemness via epigenetic activation of CRISP3 leading to lobaplatin resistance in triple-negative breast cancer. EP300通过表观遗传学激活CRISP3促进肿瘤干性，导致三阴性乳腺癌对叶铂产生耐药性。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-06-16 DOI: 10.1007/s13577-024-01091-w

Yan Wang, Yi Zhang, Xiaowei Qi

{"title":"EP300 promotes tumor stemness via epigenetic activation of CRISP3 leading to lobaplatin resistance in triple-negative breast cancer.","authors":"Yan Wang, Yi Zhang, Xiaowei Qi","doi":"10.1007/s13577-024-01091-w","DOIUrl":"10.1007/s13577-024-01091-w","url":null,"abstract":"Lobaplatin shows antitumor activity against a wide range of tumors, including triple-negative breast cancer (TNBC), and has been linked to cancer stem cell pool. Here, we investigated the molecular mechanisms behind lobaplatin resistance and stemness in vitro and in vivo. Two chemoresistance-related GEO data sets (GSE70690 and GSE103115) were included to screen out relevant genes. Cysteine-rich secretory protein 3 (CRISP3) was found to be overexpressed in lobaplatin-resistant TNBC and related to poor diagnosis. CRISP3 expression was significantly correlated with tumor stemness markers in lobaplatin-resistant cells. E1A-associated protein p300 (EP300) regulated CRISP3 expression by affecting the H3K27ac modification of the CRISP3 promoter. In addition, knocking down EP300 curbed the malignant biological behavior of lobaplatin-resistant cells, which was antagonized by CRISP3 overexpression. Collectively, our results highlight the EP300/CRISP3 axis as a key driver of lobaplatin resistance in TNBC and suggest that therapeutic targeting of this axis may be an effective strategy for enhancing platinum sensitivity in TNBC.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIN17 functions in DNA damage repair and chemosensitivity by modulating RAD51 in hepatocellular carcinoma. KIN17 通过调节肝癌中的 RAD51 在 DNA 损伤修复和化疗敏感性中发挥作用

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-06-27 DOI: 10.1007/s13577-024-01096-5

Xueran Huang, Zichang Dai, Biyun Zeng, Xiangyan Xiao, Kashif Rafiq Zahid, Xiaocong Lin, Tiancai Liu, Tao Zeng

{"title":"KIN17 functions in DNA damage repair and chemosensitivity by modulating RAD51 in hepatocellular carcinoma.","authors":"Xueran Huang, Zichang Dai, Biyun Zeng, Xiangyan Xiao, Kashif Rafiq Zahid, Xiaocong Lin, Tiancai Liu, Tao Zeng","doi":"10.1007/s13577-024-01096-5","DOIUrl":"10.1007/s13577-024-01096-5","url":null,"abstract":"The limited response of hepatocellular carcinoma (HCC) to chemotherapy drugs has always been a bottleneck in therapy. DNA damage repair is a major reason for chemoresistance. Previous studies have confirmed that KIN17 affects chemosensitivity. In this study, we examined the impact of KIN17 on chemotherapy response and DNA repair in HCC cells treated with oxaliplatin (L-OHP). We evaluated the expression and biological roles of KIN17 in HCC using bioinformatic analysis. The correlation between KIN17 and RAD51, particularly their nuclear expression levels, was evaluated using immunofluorescence, immunoblotting after nucleocytoplasmic separation in HCC cells, and immunohistochemistry of mouse xenograft tumors and human HCC tissues. The results indicated a significant increase in KIN17 expression in HCC tissues compared to normal tissues. The GSEA analysis revealed that upregulation of KIN17 was significantly associated with DNA damage repair. Knockdown of KIN17 led to increased DNA damage and reduced cellular survival after exposure to L-OHP. On the other hand, overexpression of KIN17 was linked to decreased DNA damage and improved cell survival following L-OHP treatment. Further experiments indicated that KIN17 affects the expression of RAD51, particularly in the nucleus. KIN17 plays a crucial role in influencing the sensitivity of HCC to chemotherapy by triggering the DNA repair response. Increased expression of KIN17 is associated with a poor prognosis for HCC patients, indicating that KIN17 could serve as a prognostic marker and therapeutic target for HCC.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NR2F1 overexpression alleviates trophoblast cell dysfunction by inhibiting GDF15/MAPK axis in preeclampsia. 通过抑制 GDF15/MAPK 轴，过表达 NR2F1 可减轻子痫前期滋养层细胞的功能障碍。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-07-15 DOI: 10.1007/s13577-024-01095-6

Ke Zhang, Hailing Zhang, Bing Wang, Shanshan Gao, Caiping Sun, Cong Jia, Jinquan Cui

{"title":"NR2F1 overexpression alleviates trophoblast cell dysfunction by inhibiting GDF15/MAPK axis in preeclampsia.","authors":"Ke Zhang, Hailing Zhang, Bing Wang, Shanshan Gao, Caiping Sun, Cong Jia, Jinquan Cui","doi":"10.1007/s13577-024-01095-6","DOIUrl":"10.1007/s13577-024-01095-6","url":null,"abstract":"Abnormal functions of trophoblast cells are associated with the pathogenesis of preeclampsia (PE). Nuclear receptor subfamily 2 group F member 1 (NR2F1) acts as a transcriptionally regulator in many diseases, but its role in PE remains unknown. Hypoxia/reoxygenation (H/R)-stimulated HTR-8/SVneo cells were used to mimic PE injury in vitro. NR2F1 overexpression alleviated trophoblast apoptosis, as evidenced by the decreased number of TUNEL-positive cells and the downregulation of caspase 3 and caspase 9 expression in cells. NR2F1 overexpression increased the invasion and migration ability of HTR-8/SVneo cells, accompanied by increased protein levels of matrix metalloproteinase (MMP)-2 and MMP-9. mRNA-seq was applied to explore the underlying mechanism of NR2F1, identifying growth differentiation factor 15 (GDF15) as the possible downstream effector. Dual-luciferase reporter, ChIP-qPCR, and DNA pull-down assays confirmed that NR2F1 bound to the promoter of GDF15 and transcriptionally inhibited its expression. GDF15 overexpression increased apoptosis and decreased the ability of invasion and migration in HTR-8/SVneo cells expressing NR2F1. MAPK pathway was involved in the regulation of PE. Administration of p38 inhibitor, ERK inhibitor, and JNK inhibitor reversed the effect of simultaneous overexpression NR2F1 and GDF15 on trophoblast apoptosis, invasion, and migration. Our findings demonstrated that NR2F1 overexpression inhibited trophoblast apoptosis and promoted trophoblast invasion and migration. NR2F1 might negatively regulate GDF15 expression by binding to its promoter region, which further inhibited MAPK signaling pathway in PE. Our study highlights that NR2F1 might sever as a potential target in PE.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor. 建立新型 MDM2/MYCN 共同扩增神经母细胞瘤细胞系 NBN-SHIM 并确定其特征，该细胞系由晚期复发性 MS 肿瘤建立。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI: 10.1007/s13577-024-01106-6

Keisuke Kato, Jun-Ichi Nagai, Hiroaki Goto, Masato Shinkai, Norihiko Kitagawa, Yasunori Toyoda, Toshiji Nishi, Hisato Kigasawa, Mio Tanaka, Kenji Kurosawa, Yumi Ito, Masayuki Haruta, Takehiko Kamijo, Ai Yoshimi, Masahiro Tsuchida, Noriyuki Nagahara, Yukichi Tanaka

{"title":"Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor.","authors":"Keisuke Kato, Jun-Ichi Nagai, Hiroaki Goto, Masato Shinkai, Norihiko Kitagawa, Yasunori Toyoda, Toshiji Nishi, Hisato Kigasawa, Mio Tanaka, Kenji Kurosawa, Yumi Ito, Masayuki Haruta, Takehiko Kamijo, Ai Yoshimi, Masahiro Tsuchida, Noriyuki Nagahara, Yukichi Tanaka","doi":"10.1007/s13577-024-01106-6","DOIUrl":"10.1007/s13577-024-01106-6","url":null,"abstract":"The biological heterogeneity of neuroblastoma underscores the need for an in vitro model of each molecularly defined subgroup to investigate tumorigenesis and develop targeted therapies. We have established a permanently growing cell line from a 12-year-old girl who developed a late recurrent stage MS, MDM2-amplified neuroblastoma arising in the liver and performed histological, molecular, cytogenetic, exome, and telomere analyses of the recurrent tumor and the cell line. On histology, the recurrent tumor was immunoreactive for TP53, CDKN1A, and MDM2. A molecular cytogenetic study of the recurrent tumor revealed the amplification of MDM2 but no amplification of MYCN. The established cell line, NBM-SHIM, showed amplification of both MDM2 and MYCN on double-minute chromosomes. A copy number evaluation based on exome data confirmed the finding for MYCN and MDM2 and further identified high ploidy on CDK4 and GLI2 loci in the recurrent tumor and the cell line. The telomere maintenance mechanism on the cell line is unusual in terms of the low expression of TERT despite MYCN amplification and alternative lengthening of telomeres suggested by positive value for C-circle assay and telomere contents quantitative assay. The cell line is unique because it was established from a MYCN-nonamplified, MDM2-amplified, late-relapsed stage MS neuroblastoma, and MYCN amplification was acquired during cell culture. Therefore, the cell line is a valuable tool for investigating neuroblastoma tumorigenesis and new molecular targeted therapies for disrupted ARF-TP53-MDM2 pathway and amplification of MDM2 and CDK4.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adipose-derived stem cells modified by TWIST1 silencing accelerates rat sciatic nerve repair and functional recovery. 经TWIST1沉默修饰的脂肪源性干细胞可加速大鼠坐骨神经的修复和功能恢复。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-06-21 DOI: 10.1007/s13577-024-01087-6

Bo Chen, Leining Wang, Xiaogui Pan, Shuai Jiang, Yihe Hu

{"title":"Adipose-derived stem cells modified by TWIST1 silencing accelerates rat sciatic nerve repair and functional recovery.","authors":"Bo Chen, Leining Wang, Xiaogui Pan, Shuai Jiang, Yihe Hu","doi":"10.1007/s13577-024-01087-6","DOIUrl":"10.1007/s13577-024-01087-6","url":null,"abstract":"The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury. 通过RVG-Lamp2b修饰间充质干细胞衍生的外泌体输送神经营养素-3可减轻面神经损伤。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-09-01 Epub Date: 2024-06-11 DOI: 10.1007/s13577-024-01086-7

Wenting Bi, Xiaodan Mu, Yongfeng Li, Qingyan Sun, Lei Xiang, Min Hu, Huawei Liu

{"title":"Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury.","authors":"Wenting Bi, Xiaodan Mu, Yongfeng Li, Qingyan Sun, Lei Xiang, Min Hu, Huawei Liu","doi":"10.1007/s13577-024-01086-7","DOIUrl":"10.1007/s13577-024-01086-7","url":null,"abstract":"We aim to investigate the effect of RVG-Lamp2b-modified exosomes (exos) loaded with neurotrophin-3 (NT-3) on facial nerve injury. Exos were collected from control cells (Ctrl Exo) or bone marrow mesenchymal stem cells co-transfected with RVG-Lamp2b and NT-3 plasmids (RVG-NT-3 Exo) by gradient centrifugation and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Effect of RVG-NT-3 Exo on oxidative stress damage was determined by analysis of the morphology, viability, and ROS production of neurons. Effect of RVG-NT-3 Exo on facial nerve axotomy (FNA) was determined by detecting ROS production, neuroinflammatory reaction, microglia activation, facial motor neuron (FMN) death, and myelin sheath repair. Loading NT-3 and modifying with RVG-Lamp2b did not alter the properties of the exos. Moreover, RVG-NT-3 Exo could effectively target neurons to deliver NT-3. Treatment with RVG-NT-3 Exo lowered H2O2-induced oxidative stress damage in primary neurons and Nsc-34 cells. RVG-NT-3 Exo treatment significantly decreased ROS production, neuroinflammatory response, FMN death, and elevated microglia activation and myelin sheath repair in FNA rat models. Our findings suggested that RVG-NT-3 Exo-mediated delivery of NT-3 is effective for the treatment of facial nerve injury.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0