STEM CELLS最新文献_第8页

Cancer Stem Cells as a Therapeutic Target: Current Clinical Development and Future Prospective. 作为治疗靶点的癌症干细胞：当前的临床发展和未来展望。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad092

Alex Philchenkov, Anna Dubrovska

引用次数: 0

Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia. 急性髓性白血病中异常的脂质代谢特征

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad095

Pooja Singh, Roopak Murali, Sri Gayathri Shanmugam, Steve Thomas, Julius Scott, Sudha Warrier, Frank Arfuso, Arun Dharmarajan, Rajesh Kumar Gandhirajan

{"title":"Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.","authors":"Pooja Singh, Roopak Murali, Sri Gayathri Shanmugam, Steve Thomas, Julius Scott, Sudha Warrier, Frank Arfuso, Arun Dharmarajan, Rajesh Kumar Gandhirajan","doi":"10.1093/stmcls/sxad095","DOIUrl":"10.1093/stmcls/sxad095","url":null,"abstract":"Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"200-215"},"PeriodicalIF":5.2,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on β654-Thalassemia. 基因编辑小鼠的造血干细胞对β654-地中海贫血症的治疗效果。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad096

Dan Lu, Xiuli Gong, Xinbing Guo, Yanwen Chen, Yiwen Zhu, Yudan Fang, Qin Cai, Miao Xu, Hua Yang, Dali Li, Yitao Zeng, Fanyi Zeng

{"title":"Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on β654-Thalassemia.","authors":"Dan Lu, Xiuli Gong, Xinbing Guo, Yanwen Chen, Yiwen Zhu, Yudan Fang, Qin Cai, Miao Xu, Hua Yang, Dali Li, Yitao Zeng, Fanyi Zeng","doi":"10.1093/stmcls/sxad096","DOIUrl":"10.1093/stmcls/sxad096","url":null,"abstract":"β-thalassemia is an inherited blood disease caused by reduced or inadequate β-globin synthesis due to β-globin gene mutation. Our previous study developed a gene-edited mice model (β654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the βIVS2-654 (C > T) mutation site and the 3' splicing acceptor site at 579 and corrected abnormal β-globin mRNA splicing in the β654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from β654-ER mice on β-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted β654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the β-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from β654-ER mice on β-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"278-289"},"PeriodicalIF":5.2,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138883779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Application Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells in Renal Diseases. 间充质干细胞细胞外囊泡在肾脏疾病中的应用潜力。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad089

Enhui Li, Jia Xu, Ning Liu, Qi Xiong, Weiwei Zhang, Yizi Gong, Linlin Zhang, Yikai He, Huipeng Ge, Xiangcheng Xiao

{"title":"Application Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells in Renal Diseases.","authors":"Enhui Li, Jia Xu, Ning Liu, Qi Xiong, Weiwei Zhang, Yizi Gong, Linlin Zhang, Yikai He, Huipeng Ge, Xiangcheng Xiao","doi":"10.1093/stmcls/sxad089","DOIUrl":"10.1093/stmcls/sxad089","url":null,"abstract":"The high prevalence and complex etiology of renal diseases already impose a heavy disease burden on patients and society. In certain kidney diseases such as acute kidney injury and chronic kidney disease, current treatments are limited to slowing rather than stabilizing or reversing disease progression. Therefore, it is crucial to study the pathological mechanisms of kidney disease and discover new therapeutic targets and effective therapeutic drugs. As cell-free therapeutic strategies are continually being developed, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have emerged as a hot topic for research in the field of renal diseases. Studies have demonstrated that MSC-EVs not only reproduce the therapeutic effects of MSCs but also localize to damaged kidney tissue. Compared to MSCs, MSC-EVs have several advantages, including ease of preservation, low immunogenicity, an inability to directly form tumors, and ease of artificial modification. Exploring the detailed mechanisms of MSC-EVs by developing standardized culture, isolation, purification, and drug delivery strategies will help facilitate their clinical application in kidney diseases. Here, we provide a comprehensive overview of studies about MSC-EVs in kidney diseases and discuss their limitations at the human nephrology level.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"216-229"},"PeriodicalIF":5.2,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138456744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells. 更正：烟酰胺核苷调节 HIF-1 信号以维持和增强人牙髓干细胞的牙髓分化。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad093

引用次数: 0

Leucine-Rich Repeat Containing 15-Mediated Cell Adhesion Is Essential for Integrin Signaling in TGF-β1-Induced PDL Fibroblastic Differentiation. 在 TGF-β1 诱导的 PDL 成纤维细胞分化过程中，富亮氨酸重复序列 15 (LRRC15) 介导的细胞粘附对整合素信号转导至关重要。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad090

Hyun-Jin Kim, Dong-Jun Kim, Seong-Min Kim, Young-Joo Jang

{"title":"Leucine-Rich Repeat Containing 15-Mediated Cell Adhesion Is Essential for Integrin Signaling in TGF-β1-Induced PDL Fibroblastic Differentiation.","authors":"Hyun-Jin Kim, Dong-Jun Kim, Seong-Min Kim, Young-Joo Jang","doi":"10.1093/stmcls/sxad090","DOIUrl":"10.1093/stmcls/sxad090","url":null,"abstract":"Human periodontal ligament cells (hPDLCs) cultured from periodontal ligament (PDL) tissue contain postnatal stem cells that can be differentiated into PDL fibroblasts. We obtained PDL fibroblasts from hPDLCs by treatment with low concentrations of TGF-β1. Since the extracellular matrix and cell surface molecules play an important role in differentiation, we had previously developed a series of monoclonal antibodies against PDL fibroblast-specific cell surface molecules. One of these, the anti-PDL51 antibody, recognized a protein that was significantly upregulated in TGF-β1-induced PDL fibroblasts and highly accumulated in the PDL region of the tooth root. Mass spectrometry revealed that the antigen recognized by the anti-PDL51 antibody was leucine-rich repeat containing 15 (LRRC15), and this antibody specifically recognized the extracellular glycosylated moiety of LRRC15. Experiments presented here show that as fibroblastic differentiation progresses, increased amounts of LRRC15 localized at the cell surface and membrane. Inhibition of LRRC15 by siRNA-mediated depletion and by antibody blocking resulted in downregulation of the representative PDL fibroblastic markers. Moreover, following LRRC15 inhibition, the directed and elongated cell phenotypes disappeared, and the long processes of the end of the cell body were no longer found. Through a specific interaction between integrin β1 and LRRC15, the focal adhesion kinase signaling pathway was activated in PDL fibroblasts. Furthermore, it was shown that increased LRRC15 was important for the activation of the integrin-mediated cell adhesion signal pathway for regulation of cellular functions, including fibroblastic differentiation, proliferation, and cell migration arising from the expression of PDL-related genes in TGF-β1-induced PDL fibroblastic differentiation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"251-265"},"PeriodicalIF":5.2,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Entropy Meets Physiology: Should We Translate Aging as Disorder? 熵与生理学的结合:我们应该将衰老解读为紊乱吗?

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad084

Marco Tatullo

{"title":"Entropy Meets Physiology: Should We Translate Aging as Disorder?","authors":"Marco Tatullo","doi":"10.1093/stmcls/sxad084","DOIUrl":"10.1093/stmcls/sxad084","url":null,"abstract":"Aging is characterized by an alteration of several physiological processes and biological pathways that leads to an increased susceptibility to age-related diseases and death. Normally, multipotential stem/progenitor cells may contribute to tissue homeostasis, and to minimize the age-depending DNA damage. Scientific research has demonstrated that aging induces several complex changes affecting even the mesenchymal stromal/stem cells (MSCs) ability to self-renew, differentiate, and immunomodulate the human tissues, causing further alterations in the local microenvironment. Cellular senescence can thus be considered as an overall response to several damages. Accordingly, aging seems to create the proper conditions to decrease the tissue's metabolic performance, and the cell-to-cell communication, resulting in a progressive tissue destruction; on the other hand, the MSCs functions appear to be severely reduced. This concise review summarizes the main alterations affecting the MSCs during aging, and it also explains the role of inflammation as a key player in age-related syndromes. The hypothesis is to suggest a parallelism between the thermodynamic concept of \"entropy\" and biological aging, speculating that both can increase within irreversible systems and both lead toward an irreversible disorder; so, the question is: should we translate aging as disorder?","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"91-97"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway. BK通道耗竭通过激活MAPK/ERK通路促进脂肪细胞分化。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad082

Fang Xin, Yuan Cheng, Xinxin Wen, Jin Zhang, Xin Shi, Ping Liu, Jie Ren, Wenjing Lu, Fan Liu, Zihan Li, Xin Yan, Wei Wang, Meili Wang, Haixia Huang

{"title":"BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway.","authors":"Fang Xin, Yuan Cheng, Xinxin Wen, Jin Zhang, Xin Shi, Ping Liu, Jie Ren, Wenjing Lu, Fan Liu, Zihan Li, Xin Yan, Wei Wang, Meili Wang, Haixia Huang","doi":"10.1093/stmcls/sxad082","DOIUrl":"10.1093/stmcls/sxad082","url":null,"abstract":"The expression of large conductance calcium-activated potassium channels (BK channels) in adipose tissue has been identified for years. BK channel deletion can improve metabolism in vivo, but the relative mechanisms remain unclear. Here, we examined the effects of BK channels on the differentiation of adipose-derived stem cells (ADSCs) and the related mechanisms. BKα and β1 subunits were expressed on adipocytes. We found that both deletion of the KCNMA1 gene, encoding the pore forming α subunit of BK channels, and the BK channel inhibitor paxilline increased the expression of key genes in the peroxisome proliferator activated receptor (PPAR) pathway and promoted adipogenetic differentiation of ADSCs. We also observed that the MAPK-ERK pathway participates in BK channel deficiency-promoted adipogenic differentiation of ADSCs and that ERK inhibitors blocked the differentiation-promoting effect of BK channel deficiency. Hyperplasia of adipocytes is considered beneficial for metabolic health. These results indicate that BK channels play an important role in adipose hyperplasia by regulating the differentiation of ADSCs and may become an important target for studying the pathogenesis and treatment strategies of metabolic disorder-related diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"146-157"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells. 烟酰胺核苷调节HIF-1信号传导以维持和增强人牙髓干细胞成牙细胞分化。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad083

Peimeng Zhan, Xinfang Zhang, Zhuo Xie, Lingling Chen, Shuheng Huang, Qiting Huang, Zhengmei Lin, Runfu Wang

{"title":"Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells.","authors":"Peimeng Zhan, Xinfang Zhang, Zhuo Xie, Lingling Chen, Shuheng Huang, Qiting Huang, Zhengmei Lin, Runfu Wang","doi":"10.1093/stmcls/sxad083","DOIUrl":"10.1093/stmcls/sxad083","url":null,"abstract":"Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"116-127"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA Damage Response After Treatment of Cycling and Quiescent Cord Blood Hematopoietic Stem Cells With Distinct Genotoxic Noxae. 不同基因毒性的脐带血造血干细胞循环和静止后的DNA损伤反应。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad085

Fabienne Becker, Meryem Ouzin, Stefanie Liedtke, Katharina Raba, Gesine Kogler

{"title":"DNA Damage Response After Treatment of Cycling and Quiescent Cord Blood Hematopoietic Stem Cells With Distinct Genotoxic Noxae.","authors":"Fabienne Becker, Meryem Ouzin, Stefanie Liedtke, Katharina Raba, Gesine Kogler","doi":"10.1093/stmcls/sxad085","DOIUrl":"10.1093/stmcls/sxad085","url":null,"abstract":"Hematopoietic stem cells (HSC) from cord blood can be applied as an alternative to bone marrow in transplantation to treat hematological diseases. Umbilical cord blood (UCB) consists of cycling and non-cycling CD34+/CD45low cells needed for long-term and short-term engraftment. After sorting and subsequent in vitro culture, quiescent HSCs enter the cell cycle. This enables the analysis of HSCs in 2 different cell cycle stages and the comparison of their responses to different genotoxic noxae. To analyze different mechanisms of DNA damage induction in cells, 2 different genotoxins were compared: etoposide, a topoisomerase II inhibitor that targets mitosis in the S/G2-phase of the cell cycle and the alkylating nitrosamine N-Nitroso-N-methylurea (MNU), which leads to the formation of methyl DNA adducts resulting in DNA double breaks during DNA replication and persistent mutations. Cycling cells recovered after treatment even with higher concentrations of etoposide (1.5µM/ 5µM/10µM), while sorted cells treated with MNU (0.1mM/0.3mM/0.5mM/1mM/3Mm/ 5mM) recovered after treatment with the lower MNU concentrations whereas high MNU concentrations resulted in apoptosis activation. Quiescent cells were not affected by etoposide treatment showing no damage upon entry into the cell cycle. Treatment with MNU, similarly to the cycling cells, resulted in a dose-dependent cell death. In conclusion, we found that depending on the genotoxic trigger and the cycling status, CD34+cells have distinct responses to DNA damage. Cycling cells employ both DDR and apoptosis mechanisms to prevent damage accumulation. Quiescent cells predominantly undergo apoptosis upon damage, but their cell cycle status protects them from certain genotoxic insults.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"158-171"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0