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Application potential of extracellular vesicles derived from mesenchymal stem cells in renal diseases. STEM CELLS (IF 5.2) Pub Date : 2023-11-30 Enhui Li,Jia Xu,Ning Liu,Qi Xiong,Weiwei Zhang,Yizi Gong,Linlin Zhang,Yikai He,Huipeng Ge,Xiangcheng Xiao
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 (AKI) and chronic kidney disease (CKD), 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
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Vascularized Brain Assembloids with Enhanced Cellular Complexity Provide Insights into The Cellular Deficits of Tauopathy. STEM CELLS (IF 5.2) Pub Date : 2023-11-23 Xiaohuan Sun,Simeon Kofman,Victor C Ogbolu,Celeste M Karch,Larisa Ibric,Liang Qiang
Advanced technologies have enabled the engineering of self-organized 3-dimensional (3D) cellular structures from human induced pluripotent stem cells (hiPSCs), namely organoids, which recapitulate some key features of tissue development and functions of the human central nervous system (CNS). While hiPSC-derived 3D CNS organoids hold promise in providing a human-specific platform for studying CNS development
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Procoagulant Properties of Mesenchymal Stem Cells and Extracellular Vesicles: A Novel Aspect of Thrombosis Pathogenesis. STEM CELLS (IF 5.2) Pub Date : 2023-11-15 Bianlei Yang,Yaoying Long,Anyuan Zhang,Hongxiang Wang,Zhichao Chen,Qiubai Li
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and secrete extracellular vesicles (EVs) that transport bioactive molecules and mediate intercellular communication. MSCs and MSC-derived EVs (MSC-EVs) have shown promising therapeutic effects in several diseases. However, their procoagulant activity and thrombogenic risk may limit their clinical safety
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DNA damage response after treatment of cycling and quiescent cord blood hematopoietic stem cells with distinct genotoxic noxae. STEM CELLS (IF 5.2) Pub Date : 2023-11-14 Fabienne Becker,Meryem Ouzin,Stefanie Liedtke,Katharina Raba,Gesine Kogler
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 two
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BK channel depletion promotes adipocyte differentiation by activating the MAPK/ERK pathway. STEM CELLS (IF 5.2) Pub Date : 2023-11-11 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
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
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Nicotinamide riboside modulates HIF-1 signaling to maintain and enhance odontoblastic differentiation in human dental pulp stem cells. STEM CELLS (IF 5.2) Pub Date : 2023-11-11 Peimeng Zhan,Xinfang Zhang,Zhuo Xie,Lingling Chen,Shuheng Huang,Qiting Huang,Zhengmei Lin,Runfu Wang
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
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Entropy meets Physiology: should we translate Ageing as Disorder? STEM CELLS (IF 5.2) Pub Date : 2023-11-11 Marco Tatullo
Ageing is characterized by an alteration of several physiological processes and biological pathways that leads to an incremented susceptibility to age-related diseases and death. Normally, multipotential stem/progenitor cells may contribute to tissues homeostasis, and to minimize the age-depending DNA damages. Scientific research has demonstrated that ageing induces several complex changes affecting
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CGMP Compliant Microfluidic Transfection of Induced Pluripotent Stem Cells for CRISPR-Mediated Genome Editing. STEM CELLS (IF 5.2) Pub Date : 2023-11-05 Laura R Bohrer,Nicholas E Stone,Allison T Wright,Sewoon Han,Ian Sicher,Todd A Sulchek,Robert F Mullins,Budd A Tucker
Inherited retinal degeneration is a term used to describe heritable disorders that result from the death of light sensing photoreceptor cells. Although we and others believe that it will be possible to use gene therapy to halt disease progression early in its course, photoreceptor cell replacement will likely be required for patients who have already lost their sight. While advances in autologous photoreceptor
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Improved Cryopreservation of Human Induced Pluripotent Stem Cell (iPSC) and iPSC-derived Neurons Using Ice-Recrystallization Inhibitors. STEM CELLS (IF 5.2) Pub Date : 2023-11-05 Salma Alasmar,Jez Huang,Karishma Chopra,Ewa Baumann,Amy Aylsworth,Melissa Hewitt,Jagdeep K Sandhu,Joseph S Tauskela,Robert N Ben,Anna Jezierski
Human induced pluripotent stem cells (iPSCs) and iPSC-derived neurons (iPSC-Ns) represent a differentiated modality toward developing novel cell-based therapies for regenerative medicine. However, the successful application of iPSC-Ns in cell-replacement therapies relies on effective cryopreservation. In this study, we investigated the role of ice recrystallization inhibitors (IRIs) as novel cryoprotectants
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Automated Generation of hiPSC-Derived Hepatic Progeny by Cost-Efficient Compounds. STEM CELLS (IF 5.2) Pub Date : 2023-11-05 Gert Vanmarcke,Jonathan Sai-Hong Chui,Axelle Cooreman,Kristof De Vos,Lana Cleuren,Rob Van Rossom,Guillem García-Llorens,Teresa Izuel Idoype,Ruben Boon,Manoj Kumar Gautam,José V Castell,Pieter Annaert,Frederic Lluis,Catherine M Verfaillie
Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) hold great promise for liver disease modeling, drug discovery, and drug toxicity screens. Yet, several hurdles still need to be overcome, including among others decrease in the cost of goods to generate HLCs and automation of the differentiation process. We here describe that the use of an automated liquid handling system results
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Circulating Osteoprogenitor Cells Have a Mixed Immune and Mesenchymal Progenitor Function in Humans. STEM CELLS (IF 5.2) Pub Date : 2023-11-05 Jack Feehan,Macsue Jacques,Dmitry Kondrikov,Nir Eynon,Tissa Wijeratne,Vasso Apostolopoulos,Jeffrey M Gimble,William D Hill,Gustavo Duque
BACKGROUND Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization
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Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age. STEM CELLS (IF 5.2) Pub Date : 2023-11-05 Agnieszka J Turlo,Dean E Hammond,Kerry A Ramsbottom,Jamie Soul,Alexandra Gillen,Kieran McDonald,Mandy J Peffers
Variation in mesenchymal stromal cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs are attributed to secretion of biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome remains largely unknown. Here, we examined the influence
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Unveiling the Therapeutic Potential of Non-Coding RNAs in Stroke-Induced Tissue Regeneration. STEM CELLS (IF 5.2) Pub Date : 2023-11-05 Arshi Waseem,Abdul Quaiyoom Khan,Mohsin Ali Khan,Rehan Khan,Shahab Uddin,Johannes Boltze,Syed Shadab Raza
Stroke is a major contributor to mortality and impairment on a global scale, with few effective treatments available. Aberrant expression of various non-coding RNAs (ncRNAs) has been identified after stroke onset, impacting neurogenesis, angiogenesis, apoptosis, and autophagy. The roles and mechanisms of ncRNAs hold great promise for future ischemic stroke treatments, as they could modify stroke impact
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Single-Cell RNA Sequencing Technology Landscape in 2023. STEM CELLS (IF 5.2) Pub Date : 2023-11-02 Hui-Qi Qu,Charlly Kao,Hakon Hakonarson
Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity and the dynamics of gene expression, bearing profound significance in stem cell research. Depending on the starting materials used for analysis, scRNA-seq encompasses scRNA-seq and single-nucleus RNA sequencing (snRNA-seq). scRNA-seq excels in capturing cellular heterogeneity and characterizing rare
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The critical role of miR-130b-5p in cardiomyocyte proliferation and cardiac repair in mice after myocardial infarction. STEM CELLS (IF 5.2) Pub Date : 2023-11-02 Ke Feng,Yukang Wu,Jianguo Li,Qiaoyi Sun,Zihui Ye,Xuan Li,Xudong Guo,Jiuhong Kang
Poor proliferative capacity of adult cardiomyocytes is the primary cause of heart failure after myocardial infarction (MI), thus exploring the molecules and mechanisms that promote the proliferation of adult cardiomyocytes is crucially useful for cardiac repair after MI. Here, we found that miR-130b-5p was highly expressed in mouse embryonic and neonatal hearts and able to promote cardiomyocyte proliferation
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Selective Inhibition of mTORC1 Signaling Supports the Development and Maintenance of Pluripotency. STEM CELLS (IF 5.2) Pub Date : 2023-11-01 Jin Koo Kim,Luis G Villa-Diaz,Thomas L Saunders,Ruiz P Saul,Suraj Timilsina,Fei Liu,Yuji Mishina,Paul H Krebsbach
Insight into the molecular mechanisms governing the development and maintenance of pluripotency is important for understanding early development and the use of stem cells in regenerative medicine. We demonstrate the selective inhibition of mTORC1 signaling is important for developing the inner cell mass (ICM) and the self-renewal of human embryonic stem cells. S6K suppressed the expression and function
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Mesenchymal cells retain the specificity of embryonal origin during osteogenic differentiation. STEM CELLS (IF 5.2) Pub Date : 2023-11-01 Arseniy Lobov,Polina Kuchur,Aigul Khizhina,Anastasia Kotova,Andrei Ivashkin,Daria Kostina,Polina Klausen,Evgeniia Khokhlova,Egor Repkin,Kseniia Postnikova,Daria Perepletchikova,Evgeny Denisov,Tatiana Gerashchenko,Rashid Tikhilov,Svetlana Bozhkova,Andrey Sereda,Vitaliy Karelkin,Natella Enukashvily,Anna Malashicheva
Mesenchymal stem cells (MSCs) are widely used in therapy, but the differences between MSCs of various origins and their ability to undergo osteogenic differentiation and produce extracellular matrix are not fully understood. To address this, we conducted a comparative analysis of mesenchymal cell primary cultures from six human sources, including osteoblast-like cells from the adult femur, adipose-derived
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MSC-derived small extracellular vesicles alleviate diabetic retinopathy by delivering miR-22-3p to inhibit NLRP3 inflammasome activation. STEM CELLS (IF 5.2) Pub Date : 2023-10-17 Yueqin Chen,Genhong Yao,Jun Tong,Hairong Xie,Xinyu Zheng,Huayong Zhang,Zhenggao Xie
PURPOSE This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism. METHODS In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products
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OGT ensures survival of mouse fetal liver hematopoietic progenitors partly by regulating Bcl-xL and oxidative phosphorylation. STEM CELLS (IF 5.2) Pub Date : 2023-10-10 Shunsuke Soma,Koichi Murakami,Yumi Fukuchi,Hiroyoshi Kunimoto,Hideaki Nakajima
O-linked N-acetylglucosamine transferase (OGT) critically regulates wide variety of biological processes such as gene expression, metabolism, stress response, signaling and proteostasis. In adult hematopoiesis, OGT is crucial for differentiation of B and T cells and the maintenance of hematopoietic stem cells (HSCs). However, a role for OGT in fetal liver (FL) hematopoiesis remains unknown. To investigate
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Hydrogen Sulfide Attenuates Mesenchymal Stem Cell Aging Progress via the Calcineurin-NFAT Signaling Pathway. STEM CELLS (IF 5.2) Pub Date : 2023-10-08 Shan Yang,Yingying Su,Xiaoyan Li,Hao Wang,Juan Du,Jie Feng,Yongmei Xie,Zhenhua Luo,Junji Xu,Lijia Guo,Yi Liu
Aging is a gradual process that is coupled with a decline in the regenerative capacity of stem cells and a subsequent reduction in tissue function and repair. Hydrogen sulfide (H2S) plays an important role in maintaining the function of stem cells. The present study aimed to investigate the role of H2S in mesenchymal stem cell aging and the underlying mechanism and to provide novel insights into stem
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Uncovering the Heterogeneity of Cardiac Lin-KIT+ Cells: A scRNA-seq Study on the Identification of Subpopulations. STEM CELLS (IF 5.2) Pub Date : 2023-10-08 Yan Shen,Il-Man Kim,Yaoliang Tang
The reparative potential of cardiac Lin-KIT+ (KIT) cells is influenced by their population, but identifying their markers is challenging due to changes in phenotype during in vitro culture. Resolving this issue requires uncovering cell heterogeneity and discovering new subpopulations. Single-cell RNA sequencing (scRNA-seq) can identify KIT cell subpopulations, their markers, and signaling pathways
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Cohesin Subunit RAD21 Regulates the Differentiation and Self-Renewal of Hematopoietic Stem and Progenitor Cells. STEM CELLS (IF 5.2) Pub Date : 2023-10-08 Praveen Kumar,Nenggang Zhang,John Lee,Haizi Cheng,Kristen Kurtz,Shannon E Conneely,Rajkumar Sasidharan,Rachel E Rau,Debananda Pati
Recent studies suggest that chromosomal cohesin complex proteins are important in regulating hematopoiesis and may contribute to myeloid malignancies. To investigate the effects of perturbing the cohesin subunit protein RAD21 on normal hematopoiesis, we used conditional knockout (cKO) mouse models. While cohesin is vital for hematopoietic stem cell (HSC) function, Rad21 haploinsufficiency (Rad21Δ/+)
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Stromal STAT5-Mediated Trophic Activity Regulates Hematopoietic Niche Factors. STEM CELLS (IF 5.2) Pub Date : 2023-10-08 Zhengqi Wang,Grace Emmel,Hong Seo Lim,Wandi Zhu,Astrid Kosters,Eliver E B Ghosn,Peng Qiu,Kevin D Bunting
Signal transducer and activator of transcription 5 (STAT5a and STAT5b) are intrinsically critical for normal hematopoiesis but are also expressed in stromal cells. Here, STAT5ab knockout (KO) was generated with a variety of bone marrow hematopoietic and stromal Cre transgenic mouse strains. Vav1-Cre/+STAT5abfl/fl, the positive control for loss of multipotent hematopoietic function, surprisingly dysregulated
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The Bitter Taste Receptor Agonist Denatonium Inhibits Stemness Characteristics in Hematopoietic Stem/Progenitor Cells. STEM CELLS (IF 5.2) Pub Date : 2023-10-05 Valentina Pensato,Maria Antonella Laginestra,Paolo Falvo,Stefania Orecchioni,Giovanna Talarico,Elena De Marchi,Samantha Bruno,Sara Mongiorgi,Giulia Mitola,Francesco Bertolini,Elena Adinolfi,Michele Cavo,Antonio Curti,Valentina Salvestrini
Bone marrow microenvironmental stimuli profoundly impact hematopoietic stem cell fate and biology. As G protein-coupled receptors, the bitter taste receptors (TAS2Rs) are key in transmitting extracellular stimuli into an intracellular response, within the oral cavity but also in extraoral tissues. Their expression in the bone marrow (BM)-derived cells suggests their involvement in sensing the BM microenvironmental
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Application of organoids in regenerative medicine. STEM CELLS (IF 5.2) Pub Date : 2023-09-19 Yinghua Wu,Wenrui Ye,Yong Gao,Zhenjie Yi,Zhuohui Chen,Chunrun Qu,Jing Huang,Fangkun Liu,Zhixiong Liu
Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering
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Mechanisms of Alveolar Type 2 epithelial cell death during acute lung injury. STEM CELLS (IF 5.2) Pub Date : 2023-09-16 Xiaofeng Qi,Yali Luo,Xiao Mengyong,Qiuju Zhang,Jing Luo,Linna Ma,Linfeng Ruan,Nini Lian,Liu Yongqi
Diffuse alveolar epithelial cell death occurs extensively during acute lung injury(ALI). Due to the limited proliferative capacity of alveolar type 1 epithelial (AT1)cells, the differentiation and regenerative capacity of alveolar type 2 epithelial (AT2)cells are required to restore the barrier function of alveolar epithelial cells(AECs). However, during lung injury, AT1 cells are particularly susceptible
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Transcriptional Targets of TWIST1 in Human Mesenchymal Stem/Stromal Cells Mechanistically Link Stem/Progenitor and Paracrine Functions. STEM CELLS (IF 5.2) Pub Date : 2023-09-04 Christopher L Haga,Cori N Booker,Ana Carvalho,Siddaraju V Boregowda,Donald G Phinney
Despite extensive clinical testing, mesenchymal stem/stromal cell (MSC)-based therapies continue to underperform with respect to efficacy, which reflects the paucity of biomarkers that predict potency prior to patient administration. Previously, we reported that TWIST1 predicts inter-donor differences in MSC quality attributes that confer potency. To define the full spectrum of TWIST1 activity in MSCs
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Mesenchymal stem cells promote polarization of M2 macrophages in mice with acute-on-chronic liver failure via Mertk/JAK1/STAT6 signaling. STEM CELLS (IF 5.2) Pub Date : 2023-09-02 Zhi-Hui Li,Jun-Feng Chen,Jing Zhang,Zi-Ying Lei,Li-Li Wu,Shi-Bo Meng,Jia-Lei Wang,Jing Xiong,Deng-Na Lin,Jun-Yi Wang,Zhi-Liang Gao,Bing-Liang Lin
Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured
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Engineering Critical Residues of SOX9 Discovers a Variant with Potent Capacity to Induce Chondrocytes. STEM CELLS (IF 5.2) Pub Date : 2023-08-31 Yuya Sekiguchi,Aya Fukuda,Ken Nishimura,Koji Hisatake
Articular cartilage plays vital roles as a friction minimizer and shock absorber during joint movement but has a poor capacity to self-repair when damaged through trauma or disease. Cartilage tissue engineering is an innovative technique for cartilage regeneration, yet its therapeutic application requires chondrocytes in large numbers. Direct reprogramming of somatic cells to chondrocytes by expressing
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Production and limbal lineage commitment of aniridia patient-derived induced pluripotent stem cells. STEM CELLS (IF 5.2) Pub Date : 2023-08-26 Tanja Ilmarinen,Meri Vattulainen,Jeyalakshmi Kandhavelu,Dominique Bremond-Gignac,Daniel Aberdam,Heli Skottman
Congenital aniridia is caused by heterozygous mutations on the PAX6 gene leading to reduced amount of PAX6 protein (haploinsufficiency), abnormal eye development and aniridia-associated keratopathy (AAK). This progressive corneal opacification resembles late-onset limbal stem cell (LSC) deficiency, leading to disrupted corneal epithelial renewal. The factors leading to AAK are not known and defects
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Identifying a Lung Stem Cell Subpopulation by Combining Single-Cell Morphometrics, Organoid Culture, and Transcriptomics. STEM CELLS (IF 5.2) Pub Date : 2023-08-16 Takashi Fujimura,Yasunori Enomoto,Hiroaki Katsura,Taisaku Ogawa,Saori Baba,Akira Ogata,Akira Yamaoka,Katsuyuki Shiroguchi,Mitsuru Morimoto
Single-cell RNA sequencing is a valuable tool for dissecting cellular heterogeneity in complex systems. However, it is still challenging to estimate the proliferation and differentiation potentials of subpopulations within dormant tissue stem cells. Here, we established a new single-cell analysis method for profiling the organoid-forming capacity and differentiation potential of tissue stem cells to
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hucMSCs Treatment Ameliorated Pulmonary Fibrosis via Downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 Autophagic Axis. STEM CELLS (IF 5.2) Pub Date : 2023-10-08 Ruiqiong Li,Haitong Zhang,Jinjin Zhang,Yunxia Ji,Wenbo Liu,Weili Liu,Meirong Wang,Changjun Lv,Xiaodong Song,Hongbo Li,Minge Li
This study was performed to determine the effect of human umbilical cord mesenchymal stem cells (hucMSCs) treatment on pulmonary fibrosis and investigate the circFOXP1-mediated autophagic mechanism of hucMSCs treatment. Pulmonary fibrosis models were established by spraying bleomycin in mice and TGF-β1 treatment of MRC-5 cells. Results showed that hucMSCs were retained in lung and hucMSCs treatment
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Mesenchymal Stem/Stromal Cells Therapy for Metabolic Syndrome: Potential Clinical Application? STEM CELLS (IF 5.2) Pub Date : 2023-10-08 Xiuyi Huang,Yunchong Liu,Zilun Li,Lilach O Lerman
Mesenchymal stem/stromal cells (MSCs), a class of cells with proliferative, immunomodulatory, and reparative functions, have shown therapeutic potential in a variety of systemic diseases, including metabolic syndrome (MetS). The cluster of morbidities that constitute MetS might be particularly amenable for the application of MSCs, which employ an arsenal of reparative actions to target multiple pathogenic
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In Vitro Insights Into the Influence of Marrow Mesodermal/Mesenchymal Progenitor Cells on Acute Myelogenous Leukemia and Myelodysplastic Syndromes. STEM CELLS (IF 5.2) Pub Date : 2023-09-15 Jane Liesveld,Jaques Galipeau
The study of marrow-resident mesodermal progenitors can provide important insight into their role in influencing normal and aberrant hematopoiesis as occurs in acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). In addition, the chemokine competency of these cells provides links to the inflammatory milieu of the marrow microenvironment with additional implications for normal and malignant
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Mesenchymal Stem Cells-Derived Apoptotic Extracellular Vesicles (ApoEVs): Mechanism and Application in Tissue Regeneration. STEM CELLS (IF 5.2) Pub Date : 2023-09-15 Yufan Zhu,Xihang Chen,Yunjun Liao
Mesenchymal stem cells (MSCs) are commonly used as a source for cellular therapy owing to their strong immunosuppressive and regenerative effects. However, MSCs undergo extensive apoptosis within a short period after transplantation. During apoptosis, MSCs generate several apoptotic extracellular vesicles (MSCs-ApoEVs). MSCs-ApoEVs are rich in miRNomes, metabolites, and proteomes. They are critical
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Hypoxic Preconditioning Enhances Cellular Viability and Migratory Ability: Role of DANCR/miR-656-3p/HIF-1α Axis in Placental Mesenchymal Stem Cells. STEM CELLS (IF 5.2) Pub Date : 2023-09-15 Shi Haoran,Jin Zhishan,Mao Yan,Ma Ruilin,Cui Jianjian,Yang Zejun,Zhu Jianwen,Gao Hui,Zhao Yin
Preeclampsia (PE) is a common complication of pregnancy characterized by new-onset hypertension, albuminuria, or end-stage organ dysfunction, which is seriously harmful to maternal and infant health. Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from extraembryonic mesoderm. They have the potential for self-renewal, multidirectional differentiation, immunomodulation, and tissue regeneration
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ZIC1 Dictates Osteogenesis Versus Adipogenesis in Human Mesenchymal Progenitor Cells Via a Hedgehog Dependent Mechanism. STEM CELLS (IF 5.2) Pub Date : 2023-09-15 Neelima Thottappillil,Mario A Gomez-Salazar,Mingxin Xu,Qizhi Qin,Xin Xing,Jiajia Xu,Kristen Broderick,Ji-Hye Yea,Mary Archer,Ginny Ching-Yun Hsu,Bruno Péault,Aaron W James
Numerous intrinsic factors regulate mesenchymal progenitor commitment to a specific cell fate, such as osteogenic or adipogenic lineages. Identification and modulation of novel intrinsic regulatory factors represent an opportunity to harness the regenerative potential of mesenchymal progenitors. In the present study, the transcription factor (TF) ZIC1 was identified to be differentially expressed among
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Glioblastoma Stem Cell Targeting Peptide Isolated Through Phage Display Binds Cadherin 2. STEM CELLS (IF 5.2) Pub Date : 2023-08-16 JongMyung Kim,Marine Potez,Chunhua She,Ping Huang,Qiulian Wu,Shideng Bao,Jeremy N Rich,James K C Liu
Glioblastoma stem cells (GSCs) have unique properties of self-renewal and tumor initiation that make them potential therapeutic targets. Development of effective therapeutic strategies against GSCs requires both specificity of targeting and intracranial penetration through the blood-brain barrier. We have previously demonstrated the use of in vitro and in vivo phage display biopanning strategies to
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The Effect of Vitamin D3 and Valproic Acid on the Maturation of Human-Induced Pluripotent Stem Cell-Derived Enterocyte-Like Cells. STEM CELLS (IF 5.2) Pub Date : 2023-08-16 Sylvia Leo,Yusuke Kato,Yumeng Wu,Mutsumi Yokota,Masato Koike,Shiro Yui,Kiichiro Tsuchiya,Nobuaki Shiraki,Shoen Kume
Cytochrome P450 3A4 (CYP3A4) is involved in first-pass metabolism in the small intestine and is heavily implicated in oral drug bioavailability and pharmacokinetics. We previously reported that vitamin D3 (VD3), a known CYP enzyme inducer, induces functional maturation of iPSC-derived enterocyte-like cells (iPSC-ent). Here, we identified a Notch activator and CYP modulator valproic acid (VPA), as a
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miR-486-5p Attenuates Steroid-Induced Adipogenesis and Osteonecrosis of the Femoral Head Via TBX2/P21 Axis. STEM CELLS (IF 5.2) Pub Date : 2023-07-14 Yu Chen,Boyu Tang,Weiqian Jiang,Mingjie Sun,Hongrui Zhang,Yuzhang Tao,Hongwei Wang,Dulei Xiang,Haobo Bai,Mingkang Guo,Pei Zhao,Wenlong Yan,Xiao Huang,Tingmei Chen,Chengjie Lian,Jian Zhang
Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role
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Pulsed Electromagnetic Fields Combined With Adipose-Derived Stem Cells Protect Ischemic Myocardium by Regulating miR-20a-5p/E2F1/p73 Signaling. STEM CELLS (IF 5.2) Pub Date : 2023-07-14 Yang Wang,Li Chen,Lu Wang,Gaiqin Pei,Hongxin Cheng,Qing Zhang,Shiqi Wang,Danrong Hu,Yong He,Chengqi He,Chenying Fu,Quan Wei
Myocardial infarction (MI) is a serious threat to human health. Although monotherapy with pulsed electromagnetic fields (PEMFs) or adipose-derived stem cells (ADSCs) has been reported to have positive effect on the treatment of MI, a satisfactory outcome has not yet been achieved. In recent years, combination therapy has attracted widespread interest. Herein, we explored the synergistic therapeutic
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Targeted Deletion of Rictor in BMSCs Reduces the Biological Activity of K7M2 Cells and Mitigates OS-Induced Bone Destruction. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Jinhong Lu,Dongfang Dai,Jiacheng Zhang,Rong Wang,Dengshun Miao,Weiwei Sun
Bone marrow mesenchymal stem cells (BMSCs) are indispensable cells constituting the bone marrow microenvironment that are generally recognized as being involved in the development and progression of osteosarcoma (OS). To explore whether mTORC2 signaling inhibition in BMSCs suppressed OS growth and tumor-caused bone destruction, 3-month-old littermates genotyped Rictorflox/flox or Prx1-cre; Rictorflox/flox
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Notch Signaling Regulates the Chondrogenic Potential of Both Articular Chondrocytes and Their Progenitors During Expansion. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Anastasiia D Kurenkova,Lei Li,Anna P Usanova,Xiaogang Feng,Baoyi Zhou,Andrei A Nedorubov,Alexey V Lychagin,Andrei S Chagin
Articular cartilage has a limited capacity for self-repair and clinical approaches to cartilage regeneration are needed. The only such approach developed to date involves an expansion of primary autologous chondrocytes in culture, followed by their reimplantation into a cartilage defect. However, because of the formation of fibrocartilage instead of hyaline cartilage, the outcome is often not satisfactory
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Single-Cell RNA Sequencing of Sox17-Expressing Lineages Reveals Distinct Gene Regulatory Networks and Dynamic Developmental Trajectories. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Linh T Trinh,Anna B Osipovich,Bryan Liu,Shristi Shrestha,Jean-Philippe Cartailler,Christopher V E Wright,Mark A Magnuson
During early embryogenesis, the transcription factor SOX17 contributes to hepato-pancreato-biliary system formation and vascular-hematopoietic emergence. To better understand Sox17 function in the developing endoderm and endothelium, we developed a dual-color temporal lineage-tracing strategy in mice combined with single-cell RNA sequencing to analyze 6934 cells from Sox17-expressing lineages at embryonic
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Endogenous Bone Marrow-Derived Stem Cell Mobilization and Homing for In Situ Tissue Regeneration. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Yunzi Chen,Ye Li,Feng Lu,Ziqing Dong
In mammals, post-injury repair and regenerative events rely predominantly on stem cell function. Stem cell transplantation has achieved considerable success in animals but remains unfavorable for humans because of the unavoidable drawbacks. Nevertheless, substantial evidence suggests the regenerative potential of endogenous stem cells can be improved for functional and structural recovery of tissue
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Subconjunctival Administration of Mesenchymal Stem Cells Alleviates Ocular Inflammation in a Murine Model of Corneal Alkali Burn. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Mingxiong Chen,Xiaoniao Chen,Xiaoqi Li,Junyi Wang,Jie Wu,Qun Wang,Yifei Huang,Zongjin Li,Liqiang Wang
Corneal alkali burns cause extensive damage not only to the cornea but also to the intraocular tissues. As an anti-inflammatory therapy, subconjunctival administration of mesenchymal stem cells (MSCs) for corneal protection after corneal alkali burn has been explored. Little evidence demonstrates the potential of subconjunctival MSCs delivery in protecting the post-burn intraocular tissues. This study
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Liver Disease and Cell Therapy: Advances Made and Remaining Challenges. STEM CELLS (IF 5.2) Pub Date : 2023-08-16 Sheeba Khan,Sara Mahgoub,Nada Fallatah,Patricia F Lalor,Philip N Newsome
The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant
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Neuroprotective Effects of Genome-Edited Human iPS Cell-Derived Neural Stem/Progenitor Cells on Traumatic Brain Injury. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Ryotaro Imai,Ryota Tamura,Masahiro Yo,Mizuto Sato,Mariko Fukumura,Kento Takahara,Yoshitaka Kase,Hideyuki Okano,Masahiro Toda
Despite developing neurosurgical procedures, few treatment options have achieved functional recovery from traumatic brain injury (TBI). Neural stem/progenitor cells (NS/PCs) may produce a long-term effect on neurological recovery. Although induced pluripotent stem cells (iPSCs) can overcome ethical and practical issues of human embryonic or fetal-derived tissues in clinical applications, the tumorigenicity
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SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Mark C Wilkes,Hee-Don Chae,Vanessa Scanlon,Alma-Martina Cepika,Ethan P Wentworth,Mallika Saxena,Ascia Eskin,Zugen Chen,Bert Glader,Maria Grazia Roncarolo,Stanley F Nelson,Kathleen M Sakamoto
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome associated with severe anemia, congenital malformations, and an increased risk of developing cancer. The chromatin-binding special AT-rich sequence-binding protein-1 (SATB1) is downregulated in megakaryocyte/erythroid progenitors (MEPs) in patients and cell models of DBA, leading to a reduction in MEP expansion. Here we demonstrate
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Basic Fibroblast Growth Factor Promotes Mesenchymal Stem Cell Migration by Regulating Glycolysis-Dependent β-Catenin Signaling. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 Junhou Lu,Yu Zhang,Dongyan Wang,Xiaojing Xu,Jianwei Xu,Xinyu Yang,Hongxiang Qian,Huanxiang Zhang
Migration of mesenchymal stem cells (MSCs) to the site of injury is crucial in transplantation therapy. Studies have shown that cell migration is regulated by the cellular microenvironment and accompanied by changes in cellular metabolism. However, limited information is available about the relationship between MSC migration and cellular metabolism. Here, we show that basic fibroblast growth factor
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Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Eric W Martin,Alessandra Rodriguez Y Baena,Roman E Reggiardo,Atesh K Worthington,Connor S Mattingly,Donna M Poscablo,Jana Krietsch,Michael T McManus,Susan Carpenter,Daniel H Kim,E Camilla Forsberg
Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades
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Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Marwa Mahmoud,Miia Juntunen,Amna Adnan,Laura Kummola,Ilkka S Junttila,Minna Kelloniemi,Tuula Tyrväinen,Heini Huhtala,Abeer I Abd El Fattah,Khalda Amr,Alaa Mohamad El Erian,Mimmi Patrikoski,Susanna Miettinen
For adipose stromal/stem cell (ASCs)-based immunomodulatory therapies, it is important to study how donor characteristics, such as obesity and type 2 diabetes (T2D), influence ASCs efficacy. Here, ASCs were obtained from 2 groups, donors with T2D and obesity (dASCs) or nondiabetic donors with normal-weight (ndASCs), and then cultured with anti-CD3/CD28-stimulated allogeneic CD4 T cells. ASCs were studied
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Roles and Heterogeneity of Mesenchymal Progenitors in Muscle Homeostasis, Hypertrophy, and Disease. STEM CELLS (IF 5.2) Pub Date : 2023-06-15 So-Ichiro Fukada,Akiyoshi Uezumi
Skeletal muscle is mainly composed of multinucleated cells called myofibers and has excellent regenerative and adaptive abilities. These abilities are granted by muscle satellite cells (MuSCs), which are anatomically defined cells located between myofibers and basal lamina. In addition to myofibers and MuSCs, skeletal muscle contains several types of cells located in interstitial areas, such as mesenchymal
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Revisiting the Mesenchymal "Stem vs. Stromal" Cell Dichotomy and Its Implications for Development of Improved Potency Metrics. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Donald G Phinney,Ryang Hwa Lee,Siddaraju V Boregowda
Mesenchymal stem/stromal cell (MSC)-based therapies have been evaluated in over 1500 human clinical trials for a diverse array of disease indication, but outcomes remain unpredictable due to knowledge gaps in the quality attributes that confer therapeutic potency onto cells and their mode of action in vivo. Based on accumulated evidence from pre-clinical models, MSCs exert therapeutic effects by repressing
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Lineage Tracing of RGS5-CreER-Labeled Cells in Long Bones During Homeostasis and Injury. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Sierra H Root,Ivana Vrhovac Madunic,Mark S Kronenberg,Ye Cao,Sanja Novak,Ivo Kalajzic
Regulator of G protein signaling 5 (RGS5) is a GTPase activator for heterotrimeric G-protein α-subunits, shown to be a marker of pericytes. Bone marrow stromal cell population (BMSCs) is heterogeneous. Populations of mesenchymal progenitors, cells supportive of hematopoiesis, and stromal cells regulating bone remodeling have been recently identified. Periosteal and bone marrow mesenchymal stem cells
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Very Small Embryonic-Like Stem Cells Transform Into Cancer Stem Cells and Are Novel Candidates for Detecting/Monitoring Cancer by a Simple Blood Test. STEM CELLS (IF 5.2) Pub Date : 2023-04-25 Deepa Bhartiya,Nripen Sharma,Shruti Dutta,Piyush Kumar,Ashish Tripathi,Anish Tripathi
Cancer continues to remain a "Black Box," as there is no consensus on how it initiates, progresses, metastasizes, or recurs. Many imponderables exist about whether somatic mutations initiate cancer, do cancer stem cells (CSCs) exist, and if yes, are they a result of de-differentiation or originate from tissue-resident stem cells; why do cancer cells express embryonic markers, and what leads to metastasis
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Metabolic Rewiring and Stemness: A Critical Attribute of Pancreatic Cancer Progression. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Ayoola O Ogunleye,Rama Krishna Nimmakayala,Surinder K Batra,Moorthy P Ponnusamy
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive diseases with a poor 5-year survival rate. PDAC cells rely on various metabolic pathways to fuel their unlimited proliferation and metastasis. Reprogramming glucose, fatty acid, amino acid, and nucleic acid metabolisms contributes to PDAC cell growth. Cancer stem cells are the primary cell types that play a critical role in the progression
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Manipulation of Signal Gradient and Transcription Factors Recapitulates: Multiple Hypothalamic Identities. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Maho Yamamoto,Agnes Lee Chen Ong,Takuma Shinozuka,Manabu Shirai,Noriaki Sasai
During development, the hypothalamus emerges from the ventral diencephalon and is regionalized into several distinct functional domains. Each domain is characterized by a different combination of transcription factors, including Nkx2.1, Nkx2.2, Pax6, and Rx, which are expressed in the presumptive hypothalamus and its surrounding regions, and play critical roles in defining each area. Here, we recapitulated
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ASCs Activate cGAS-Type I IFNs-IL-7 Axis Via Pseudomonas aeruginosa-Derived Outer Membrane Vesicles to Resolve Pneumonia. STEM CELLS (IF 5.2) Pub Date : 2023-05-15 Caixia Di,Yanshan Jiang,Lulu Li,Mengmeng Shi,Yinggang Zhu,Jing Zhang,Yuanlin Song,Xiao Su,Jieming Qu
Mesenchymal stem cells (MSCs) therapy could efficiently attenuate LPS-induced acute lung injury and Pseudomonas aeruginosa (PA)-induced acute pneumonia. However, the underlying molecular mechanisms are still elusive. Here, we report that PA-derived outer membrane vesicles (OMVs) trigger mouse primary adipose tissue-derived mesenchymal stem cells (ASCs) to upregulate cyclic GMP-AMP synthase (cGAS) for