Lucas K Smith, Evgenia Verovskaya, Gregor Bieri, Alana M Horowitz, Saskia N I von Ungern-Sternberg, Karin Lin, Peter Seizer, Emmanuelle Passegué, Saul A Villeda
The aged systemic milieu promotes cellular and cognitive impairments in the hippocampus. Here, we report that aging of the hematopoietic system directly contributes to the pro-aging effects of old blood on cognition. Using a heterochronic hematopoietic stem cell (HSC) transplantation model (in which the blood of young mice is reconstituted with old HSCs), we find that exposure to an old hematopoietic system inhibits hippocampal neurogenesis, decreases synaptic marker expression, and impairs cognition. We identify a number of factors elevated in the blood of young mice reconstituted with old HSCs, of which cyclophilin A (CyPA) acts as a pro-aging factor...
August 2020: Aging Cell
Jie Hao, Jiani Cao, Lei Wang, Aijin Ma, Si Chen, Jinfeng Ding, Liu Wang, Boqiang Fu, Yu Zhang, Xuetao Pei, Peng Xiang, Qiyuan Li, Yong Zhang, Jiaxi Zhou, Shijun Hu, Junying Yu, Jun Wei, Huanxin Zhu, Glyn Stacey, Tongbiao Zhao, Qi Zhou
'Requirements for Human Embryonic Stem Cells' is the first set of guidelines on human embryonic stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements and transportation requirements for human embryonic stem cells, which is applicable to the quality control for human embryonic stem cells...
October 19, 2020: Cell Proliferation
Yixi Chen, Tilo Kunath, Joanna Simpson, Natalie Homer, Sergiy Sylantyev
Human embryonic stem cell (hESC)-derived midbrain dopamine (DA) neurons stand out as a cell source for transplantation with their sustainability and consistency superior to the formerly used fetal tissues. However, multiple studies of DA neurons in culture failed to register action potential (AP) generation upon synaptic input. To test whether this is due to deficiency of NMDA receptor (NMDAR) coagonists released from astroglia, we studied the functional properties of neural receptors in hESC-derived DA neuronal cultures...
August 16, 2020: FEBS Letters
Alessandro Jäger, Ricardo K Donato, Magdalena Perchacz, Katarzyna Z Donato, Zdeněk Starý, Rafał Konefał, Magdalena Serkis-Rodzeń, Maria G Raucci, Alexandre M Fuentefria, Eliézer Jäger
The advances in polymer chemistry have allowed the preparation of biomedical polymers using human metabolites as monomers that can hold unique properties beyond the required biodegradability and biocompatibility. Herein, we demonstrate the use of endogenous human metabolites (succinic and dilinoleic acids) as monomeric building blocks to develop a new series of renewable resource-based biodegradable and biocompatible copolyesters. The novel copolyesters were characterized in detail employing several standard techniques, namely 1H NMR, 13C NMR, and FTIR spectroscopy and SEC, followed by an in-depth thermomechanical and surface characterization of their resulting thin films (DSC, TGA, DMTA, tensile tests, AFM, and contact angle measurements)...
October 19, 2020: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Hiroyuki Takamura, Ryousuke Gabata, Yoshinao Obatake, Shinichi Nakanuma, Hironori Hayashi, Kazuto Kozaka, Motoko Sasaki, Mitsuyoshi Okazaki, Takahisa Yamaguchi, Hiroyuki Shimbashi, Shiro Terai, Koichi Okamoto, Isamu Makino, Jun Kinoshita, Keishi Nakamura, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Sachio Fushida, Azusa Kitao, Masaaki Kitahara, Kuniaki Arai, Taro Yamashita, Tatsuya Yamashita, Hiroko Ikeda, Yasunori Satoh, Kenichi Harada, Syuichi Kaneko, Toshihumi Gabata, Tateo Kosaka, Tetsuo Ohta
BACKGROUND AND OBJECTIVES: Although cholangiolocellular carcinoma is considered a combined hepatocellular and cholangiocarcinoma, we feel that this classification is not appropriate. Therefore, we compared the diagnostic imaging findings, surgical prognosis, and pathological features of cholangiolocellular carcinoma with those of other combined hepatocellular and cholangiocarcinoma subtypes, hepatocellular carcinoma, and cholangiocarcinoma. METHODS: The study patients included 7 with classical type combined hepatocellular and cholangiocarcinoma; 8 with stem cell feature, intermediate type combined hepatocellular and cholangiocarcinoma; 13 with cholangiolocellular carcinoma; 58 with cholangiocarcinoma; and 359 with hepatocellular carcinoma...
January 2020: Technology in Cancer Research & Treatment
H Z Shi, J C Zeng, S H Shi, H Giannakopoulos, Q Z Zhang, A D Le
Healthy aging is a complex biological process with progressive accumulation of senescent cells characterized by stable cell cycle arrest, resulting in impaired homeostasis, regenerative potential, and gradual functional decline in multiple tissues and organs, whereby the aberrant activation of mammalian target of rapamycin (mTOR) signaling networks plays a central role. Herein, we explored the effects of extracellular vesicles (EVs) released by gingiva-derived mesenchymal stem cells (GMSC-EVs) on oxidative stress-induced cellular senescence in human endothelial cells and skin fibroblasts and their antiaging potentials...
October 17, 2020: Journal of Dental Research
T Nakano, K A Warner, A E Oklejas, Z Zhang, C Rodriguez-Ramirez, A G Shuman, J E Nör
Patients with advanced salivary gland mucoepidermoid carcinoma (MEC) are treated with surgery and radiotherapy, as current systemic therapies are largely ineffective. As such, current treatment frequently leads to poor long-term survival due to locoregional recurrence or metastases. We have shown that salivary gland cancer stem cells (CSCs) are resistant to platinum-based chemotherapy and drive tumor progression. The purpose of this study was to investigate the effect of therapeutic inhibition of mTOR (mechanistic target of rapamycin) on resistance of CSCs to cisplatin, a prototypic platinum-based chemotherapeutic agent...
October 17, 2020: Journal of Dental Research
Ioanna Eleftheriadou, Georgia Samakidou, Anastasios Tentolouris, Nikolaos Papanas, Nikolaos Tentolouris
Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes mellitus that is associated with increased morbidity and mortality, as well as substantial economic burden for the health care system. The standard of care for DFUs includes pressure off-loading, sharp debridement, and wound moisture balance, along with infection control and management of peripheral arterial disease. A variety of advanced modalities that target distinct pathophysiological aspects of impaired wound healing in diabetes are being studied as possible adjunct therapies for difficult to heal ulcers...
October 19, 2020: International Journal of Lower Extremity Wounds
Wanyi Ye, Xueting Kong, Wenbin Zhang, Zheng Weng, Xiuli Wu
The αβ T-cell-depleted hematopoietic stem cell transplantation (HSCT) leads to lower relapse and better outcome, and may correlate strongly with expansion of donor-derived γδ T cells. γδ T cells play an important role in immune reconstitution and can exert a graft-versus-leukemia effect after HSCT. This review showed the recent literature on immune functions of γδ T cells after HSCT. The discrepancies between studies of γδ T cells in graft-versus-host disease may cause by its heterogeneous and various distinct subsets...
January 2020: Cell Transplantation
Yang Wu, Bugra Ayan, Kazim K Moncal, Youngnam Kang, Aman Dhawan, Srinivas V Koduru, Dino J Ravnic, Fadia Kamal, Ibrahim T Ozbolat
The heterogeneous and anisotropic articular cartilage is generally studied as a layered structure of "zones" with unique composition and architecture, which is difficult to recapitulate using current approaches. A novel hybrid bioprinting strategy is presented here to generate zonally stratified cartilage. Scaffold-free tissue strands (TSs) are made of human adipose-derived stem cells (ADSCs) or predifferentiated ADSCs. Cartilage TSs with predifferentiated ADSCs exhibit improved mechanical properties and upregulated expression of cartilage-specific markers at both transcription and protein levels as compared to TSs with ADSCs being differentiated in the form of strands and TSs of nontransfected ADSCs...
October 19, 2020: Advanced Healthcare Materials
Vedat Uygun, Gülsün Karasu, Hayriye Daloğlu, Seda Öztürkmen, Koray Yalçın, Safiye Suna Çelen, Akif Yeşilipek
Although advancements have been made in monitoring and preventing viral infections in HSCT patients, CMV reactivation still remains a critical post-transplant complication. Adoptive cell therapy is an alternative to pharmacotherapy of CMV infection in refractory patients. We retrospectively reviewed CMV infection cases after allogeneic HSCT who received U-DLI as treatment. In total, five pediatric patients between the ages of 0.5-16 years that received U-DLI for a post-HSCT CMV infection were evaluated. The dose of CD3+ lymphocytes administered in DLI was 5 × 104 /kg, except in one patient transplanted from his sibling...
October 19, 2020: Pediatric Transplantation
Shashi Kant Tiwari, Jason W Dang, Nianwei Lin, Yue Qin, Shaobo Wang, Tariq M Rana
Zika virus (ZIKV) is an emerging flavivirus, which when passed through vertical transmission from mother to developing fetus can lead to developmental abnormalities, including microcephaly. While there is mounting evidence that suggests a causal relationship between ZIKV infection and microcephaly, the mechanisms by which ZIKV induces these changes remain to be elucidated. Here, we demonstrate that ZIKV infection of neural stems cells, both in vitro and in vivo, induces macroautophagy to enhance viral replication...
October 19, 2020: EMBO Reports
Takashi Matozaki, Takenori Kotani, Yoji Murata, Yasuyuki Saito
The turnover of intestinal epithelial cells (IECs) is relatively rapid (3 to 5 days in mouse and human), and this short existence and other aspects of the homeostasis of IECs are tightly regulated by various signaling pathways including Wnt-β-catenin signaling. Dysregulation of IEC homeostasis likely contributes to the development of intestinal inflammation and intestinal cancer. The roles of receptor protein tyrosine kinases and their downstream signaling molecules such as Src family kinases, Ras, and mammalian target of rapamycin (mTOR) in homeostatic regulation of IEC turnover have recently been evaluated...
October 18, 2020: Cancer Science
Michael Ankcorn, Bengü Said, Dilys Morgan, Ahmed M Elsharkawy, James Maggs, Stephen Ryder, Talal Valliani, Fiona Gordon, Kushala Abeysekera, Deepak Suri, Stuart McPherson, Jack Galliford, Belinda Smith, Emanuela Pelosi, Sanjay Bansal, Claire Bethune, David Sheridan, Louisa Vine, Richard S Tedder, Samreen Ijaz
The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data was recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70...
October 18, 2020: Journal of Viral Hepatitis
Hirofumi Watanabe, Kazunori Kanemaru, Kazuhiro Hagikura, Taro Matsumoto, Mamoru Ayusawa, Ichiro Morioka
Interactions between tissues such as epicardial adipose (EAT), and myocardial tissues is important in the pathogenesis of heart failure. Changes in adipose tissues in obesity or diabetes impair preadipocyte differentiation. Furthermore, pro-inflammatory cytokine secretion is higher in preadipocytes than in mature adipocytes in diabetes and obesity. However, how undifferentiated cells committed to the adipose lineage directly influence cardiomyocytes is not yet understood. We used human-derived dedifferentiated fat (DFAT) cells as models of undifferentiated cells committed to an adipose lineage...
October 19, 2020: Cell Biology International
Hyuck Hoon Kwon, Steven Hoseong Yang, Joon Lee, Byung Chul Park, Kui Young Park, Jae Yoon Jung, Youin Bae, Gyeong-Hun Park
A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation...
October 19, 2020: Acta Dermato-venereologica
Aaron Zhong, Mu Li, Ting Zhou
Reporter cell lines based on human pluripotent stem cells (hPSCs) are highly desirable for studying differentiation, lineage tracing, and target cell selection. However, several technical bottlenecks, such as DNA transduction, low homology recombination rate (HDR), and single-cell cloning, have made this effort an arduous process in hPSCs. Here, we provide a step-by-step protocol and practical guide for generating reporter lines in hPSCs via CRISPR/Cas9-mediated HDR. We also elaborate on the process of generating a TBXT-GFP reporter line as an example...
September 18, 2020: STAR protocols
Anna Lm Smith, Julia C Whitehall, Carla Bradshaw, David Gay, Fiona Robertson, Alasdair P Blain, Gavin Hudson, Angela Pyle, David Houghton, Matthew Hunt, James N Sampson, Craig Stamp, Grace Mallett, Shoba Amarnath, Jack Leslie, Fiona Oakley, Laura Wilson, Angela Baker, Oliver M Russell, Riem Johnson, Claire A Richardson, Bhavana Gupta, Iain McCallum, Stuart Ac McDonald, Seamus Kelly, John C Mathers, Rakesh Heer, Robert W Taylor, Neil D Perkins, Doug M Turnbull, Owen J Sansom, Laura C Greaves
Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA (mtDNA) mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumours, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mtDNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting they may confer a metabolic advantage. To test this we deleted the tumour suppressor Apc in OXPHOS deficient intestinal stem cells in mice...
October 2020: Nature cancer
Aubrey L Miller, Patrick L Garcia, Tracy L Gamblin, Rebecca B Vance, Karina J Yoon
Aim: Gemcitabine is a frontline agent for locally-advanced and metastatic pancreatic ductal adenocarcinoma (PDAC), but neither gemcitabine alone nor in combination produces durable remissions of this tumor type. We developed three PDAC patient-derived xenograft (PDX) models with gemcitabine resistance (gemR) acquired in vivo , with which to identify mechanisms of resistance relevant to drug exposure in vivo and to evaluate novel therapies. Methods: Mice bearing independently-derived PDXs received 100 mg/kg gemcitabine once or twice weekly...
2020: Cancer Drug Resistance
Nihar Kinarivala, Ahmed Morsy, Ronak Patel, Angelica V Carmona, Md Sanaullah Sajib, Snehal Raut, Constantinos M Mikelis, Abraham Al-Ahmad, Paul C Trippier
The neuronal ceroid lipofuscinoses (NCLs) are a family of rare lysosomal storage disorders. The most common form of NCL occurs in children harboring a mutation in the CLN3 gene. This form is lethal with no existing cure or treatment beyond symptomatic relief. The pathophysiology of CLN3 disease is complex and poorly understood, with current in vivo and in vitro models failing to identify pharmacological targets for therapeutic intervention. This study reports the characterization of the first CLN3 patient-specific induced pluripotent stem cell (iPSC)-derived model of the blood-brain barrier and establishes the suitability of an iPSC-derived neuron model of the disease to facilitate compound screening...
October 9, 2020: ACS Pharmacology & Translational Science
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