Sijia Yan, Khan Zara Ahmad, Sijie Li, Antony R Warden, Jing Su, Yu Zhang, Youyi Yu, Xiao Zhi, Xianting Ding
Advances in trace protein detection contribute to the early diagnosis of diseases and exploration of stem cell development. The pre-coated interface proximity extension reaction (PIPER) assay enables target protein detection at trace levels and was developed based on protein biomarker recognition using sets of three specific antibodies and the extension of antibody-bound nucleic acid chains in proximity, accompanied by amplification and reading of protein signals via real-time quantitative polymerase chain reaction (qPCR)...
April 6, 2021: Biosensors & Bioelectronics
Celia M Dunn, Sumako Kameishi, David W Grainger, Teruo Okano
Mesenchymal stromal cells (MSCs) have gained immense attention over the past two decades due to their multipotent differentiation potential and pro-regenerative and immunomodulatory cytokine secretory profiles. Their ability to modulate the host immune system and promote tolerance has prompted several allogeneic and autologous hMSC-based clinical trials for the treatment of graft-versus-host disease and several other immune-induced disorders. However, clinical success beyond safety is still controversial and highly variable, with inconclusive therapeutic benefits and little mechanistic explanation...
April 12, 2021: Acta Biomaterialia
Yang Liang Boo, Liang Piu Koh
Mature T- and natural killer (NK)-cell non-Hodgkin lymphoma (T-cell NHL) have a poor prognosis. Data from existing retrospective and prospective studies has suggested that high-dose chemotherapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) may improve the survival in patients with chemosensitive disease, either in the upfront or salvage setting. Auto-HCT is currently recommended to be used as frontline consolidation in peripheral T-cell lymphoma not otherwise specified (PTCL-nos), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK) negative, NK/T-cell (disseminated), and enteropathy-associated T-cell lymphoma (EATL)...
April 12, 2021: Transplantation and cellular therapy
Louise Reilly, Lee Eckhardt
Potassium inward rectifier channel Kir2 is an important component of terminal cardiac repolarization and resting membrane stability. This functionality is part of balanced cardiac excitability and is a defining feature of excitable cardiac membranes. "Gain"- or "loss-of-function" mutations in KCNJ2, the gene encoding Kir2.1, cause genetic sudden cardiac death syndromes, and loss of Kir2 current, IK1 , is a major contributing factor to arrhythmogenesis in failing human hearts. Here we provide a contemporary review of the Kir2 channels' functional structure, physiology and pharmacology...
April 12, 2021: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Masahiro Nogami, Mitsuru Ishikawa, Atsushi Doi, Osamu Sano, Takefumi Sone, Tetsuya Akiyama, Masashi Aoki, Atsushi Nakanishi, Kazuhiro Ogi, Masato Yano, Hideyuki Okano
Fused in sarcoma/translated in liposarcoma (FUS) is a causative gene of amyotrophic lateral sclerosis (ALS). Mutated FUS causes accumulation of DNA damage and cytosolic stress granule (SG) formation, thereby motor neuron (MN) death. However, key molecular aetiology remains unclear. Here, we applied a novel platform technology, iBRN, "Non- biased" Bayesian gene regulatory network analysis based on induced pluripotent stem cell (iPSC)-derived cell model, to elucidate the molecular aetiology using transcriptome of iPSC-derived MNs harboring FUSH517D ...
April 12, 2021: Neurobiology of Disease
Livia Goto-Silva, Michele Martins, Jimmy Rodriguez Murillo, Leticia Rocha, Gabriela Vitória, Júlia T Oliveira, Juliana M Nascimento, Erick Correia Loiola, Fabio C S Nogueira, Gilberto B Domont, Marília Zaluar P Guimarães, Fernanda Tovar-Moll, Stevens Kastrup Rehen, Magno Junqueira
Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain...
April 12, 2021: Biochimica et Biophysica Acta. Proteins and Proteomics
Xiaohui Chen, Shengxing Wang, Zhan Cui, Yutong Gu
AIMS: Muscle and adipose tissue-derived mesenchymal stem cells presented high osteogenic potentials, which modulate osteoblast function through releasing extracellular vesicles (EVs) containing miRNAs. Herein, this study evaluated the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) delivering miR-497-5p in ossification of the posterior longitudinal ligament (OPLL). MAIN METHODS: The expression level of miR-497-5p was validated in ossified posterior longitudinal ligament (PLL) tissues and BMSC-EVs...
April 12, 2021: Life Sciences
Anna Goddi, Liesl Schroedl, Eric M Brey, Ronald N Cohen
Laminins are extracellular matrix proteins that reside in the basement membrane and provide structural support in addition to promoting cellular adhesion and migration. Through interactions with cell surface receptors, laminins stimulate intracellular signaling cascades which direct specific survival and differentiation outcomes. In metabolic tissues such as the pancreas, adipose, muscle, and liver, laminin isoforms are expressed in discrete temporal and spatial patterns suggesting that certain isoforms may support the development and function of particular metabolic cell types...
April 12, 2021: Metabolism: Clinical and Experimental
Barbara Sarina, Pietro Mancosu, Pierina Navarria, Stefania Bramanti, Jacopo Mariotti, Chiara De Philippis, Elena Clerici, Ciro Franzese, Daniele Mannina, Viviana Valli, Carmelo Carlo-Stella, Marta Scorsetti, Armando Santoro, Luca Castagna
Low-dose total body irradiation (TBI) has long been used in nonmyeloablative conditioning (NMAC) regimens before allogeneic stem cell transplantation from haploidentical donors (haplo-SCT). More recently, the use of total marrow lymphoid irradiation (TMLI) instead of TBI in conditioning is increasing. This study aimed to evaluate outcomes in a cohort of patients treated with low-dose TMLI in terms of engraftment, full donor chimerism status, graft-versus-host disease (GVHD), and extrahematologic toxicities, and to compare these outcomes with those in a cohort of patients receiving conventional TBI-containing conditioning...
March 15, 2021: Transplantation and cellular therapy
Silvana Novelli, Leyre Bento, Irene Garcia, Laura Prieto, Lucía López, Gonzalo Gutierrez, Rafael Hernani, Ariadna Pérez, Albert Esquirol, Carlos Solano, Mariana Bastos, Nieves Dorado, Nancy Rodríguez, Guillermo Rodríguez, Jose L Piñana, Juan Montoro, Pilar Herrera, Alejandro Luna, Rocío Parody, Carmen Martín, Estefanía García, Oriana López, Inmaculada Heras, Joud Zanabili, Jose M Moraleda, Lucrecia Yañez, Antonio Gutierrez, Teresa Zudaire, Raúl Córdoba, Rosario Varela, Christelle Ferra, Joaquin Martínez, Carmen Martínez, Eva Gonzalez-Barca, Rodrigo Martino, Dolores Caballero
Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years...
March 15, 2021: Transplantation and cellular therapy
Ester Gangoso, Benjamin Southgate, Leanne Bradley, Stefanie Rus, Felipe Galvez-Cancino, Niamh McGivern, Esra Güç, Chantriolnt-Andreas Kapourani, Adam Byron, Kirsty M Ferguson, Neza Alfazema, Gillian Morrison, Vivien Grant, Carla Blin, IengFong Sou, Maria Angeles Marques-Torrejon, Lucia Conde, Simona Parrinello, Javier Herrero, Stephan Beck, Sebastian Brandner, Paul M Brennan, Paul Bertone, Jeffrey W Pollard, Sergio A Quezada, Duncan Sproul, Margaret C Frame, Alan Serrels, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment. Mechanistically, this is not elicited via genetic selection of tumor subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack...
April 9, 2021: Cell
James S Chavez, Jennifer L Rabe, Dirk Loeffler, Kelly C Higa, Giovanny Hernandez, Taylor S Mills, Nouraiz Ahmed, Rachel L Gessner, Zhonghe Ke, Beau M Idler, Katia E Niño, Hyunmin Kim, Jason R Myers, Brett M Stevens, Pavel Davizon-Castillo, Craig T Jordan, Hideaki Nakajima, John Ashton, Robert S Welner, Timm Schroeder, James DeGregori, Eric M Pietras
Hematopoietic stem cells (HSCs) are capable of entering the cell cycle to replenish the blood system in response to inflammatory cues; however, excessive proliferation in response to chronic inflammation can lead to either HSC attrition or expansion. The mechanism(s) that limit HSC proliferation and expansion triggered by inflammatory signals are poorly defined. Here, we show that long-term HSCs (HSCLT) rapidly repress protein synthesis and cell cycle genes following treatment with the proinflammatory cytokine interleukin (IL)-1...
June 7, 2021: Journal of Experimental Medicine
Jia-Hong Gong, Jiao-Yun Dong, Ting Xie, Qingnan Zhao, Shu-Liang Lu
OBJECTIVE: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments...
April 1, 2021: Journal of Wound Care
Timothy J Cashman, Chinmay M Trivedi
No abstract text is available yet for this article.
April 16, 2021: Circulation Research
Yuntong Zhang, Yang Xie, Zichen Hao, Panyu Zhou, Panfeng Wang, Shuo Fang, Lu Li, Shuogui Xu, Yan Xia
Repair of large bone defects represents a major challenge for orthopedic surgeons. The newly formed microvessels inside grafts play a crucial role in successful bone tissue engineering. Previously, an active role for mesenchymal stem cell (MSC)-derived exosomes in blood vessel development and progression was suggested in the repair of multiple tissues. However, the reports on the application of MSC-derived exosomes in the repair of large bone defects are sparse. In this study, we encapsulated umbilical MSC-derived exosomes (uMSC EXOs) in hyaluronic acid hydrogel (HA-Gel) and combined them with customized nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds to repair cranial defects in rats...
April 15, 2021: ACS Applied Materials & Interfaces
Fuad Gandhi Torizal, Hyunjin Choi, Marie Shinohara, Yasuyuki Sakai
iPSCs are potential cell types that can be used for regenerative medicine. Suspension culture is the main approach to produce a sufficient amount of required cells to realize the application of hiPSCs for the transplantation of the large organ. The dialysis culture system holds the potential to reduce the cost by utilizing endogenous growth factors and recycle the remaining exogenous growth factors at the same time. However, the current large scale dialysis culture system was not optimized for expanding the high-density culture...
April 16, 2021: Methods in Molecular Biology
Haocheng Lu, Jifeng Zhang, Y Eugene Chen, Minerva T Garcia-Barrio
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Genome-wide association studies (GWAS) are powerful epidemiological tools to find genes and variants associated with cardiovascular diseases while follow-up biological studies allow to better understand the etiology and mechanisms of disease and assign causality. Improved methodologies and reduced costs have allowed wider use of bulk and single-cell RNA sequencing, human-induced pluripotent stem cells, organoids, metabolomics, epigenomics, and novel animal models in conjunction with GWAS...
April 15, 2021: Cardiovascular Drugs and Therapy
Min Tang, Yang Chen, Bingrui Li, Hikaru Sugimoto, Sujuan Yang, Changqing Yang, Valerie S LeBleu, Kathleen M McAndrews, Raghu Kalluri
Hepatic fibrosis is a wound healing response that results in excessive extracellular matrix (ECM) accumulation in response to chronic hepatic injury. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor associated with the pathogenesis of liver fibrosis. Though a promising potential therapeutic target, there are no specific drug candidates for STAT3. Exosomes are extracellular vesicles generated by all cell types with a capacity to efficiently enter cells across different biological barriers...
May 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Matthias Kettwig, Henry Klemp, Stefan Nessler, Frank Streit, Ralph Krätzner, Hendrik Rosewich, Jutta Gärtner
X-linked adrenoleukodystrophy (X-ALD) is the most common leukodystrophy. Despite intensive research in recent years, it remains unclear, what drives the different clinical disease courses. Due to this missing pathophysiological link, therapy for the childhood cerebral disease course of X-ALD (CCALD) remains symptomatic; the allogenic hematopoietic stem cell transplantation or hematopoietic stem-cell gene therapy is an option for early disease stages. The inclusion of dried blood spot (DBS) C26:0-lysophosphatidylcholine to newborn screening in an increasing number of countries is leading to an increasing number of X-ALD patients diagnosed at risk for CCALD...
April 14, 2021: Journal of Inherited Metabolic Disease
Oisín King, Ilona Sunyovszki, Cesare M Terracciano
The myocardium is a diverse environment, requiring coordination between a variety of specialised cell types. Biochemical crosstalk between cardiomyocytes (CM) and microvascular endothelial cells (MVEC) is essential to maintain contractility and healthy tissue homeostasis. Yet, as myocytes beat, heterocellular communication occurs also through constantly fluctuating biomechanical stimuli, namely (1) compressive and tensile forces generated directly by the beating myocardium, and (2) pulsatile shear stress caused by intra-microvascular flow...
April 14, 2021: Pflügers Archiv: European Journal of Physiology
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