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https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#1
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786560/microfabrication-of-liver-and-heart-tissues-for-drug-development
#2
REVIEW
Grace E Brown, Salman R Khetani
Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784586/ultrasound-mediated-gene-delivery-enhances-tendon-allograft-integration-in-mini-pig-ligament-reconstruction
#3
Maxim Bez, Thomas J Kremen, Wafa Tawackoli, Pablo Avalos, Dmitriy Sheyn, Galina Shapiro, Joseph C Giaconi, Shiran Ben David, Jess G Snedeker, Zulma Gazit, Katherine W Ferrara, Dan Gazit, Gadi Pelled
Ligament injuries occur frequently, substantially hindering routine daily activities and sports participation in patients. Surgical reconstruction using autogenous or allogeneic tissues is the gold standard treatment for ligament injuries. Although surgeons routinely perform ligament reconstructions, the integrity of these reconstructions largely depends on adequate biological healing of the interface between the ligament graft and the bone. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would lead to significantly improved ligament graft integration...
April 26, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29784000/the-homing-of-bone-marrow-stem-cells-is-differentially-activated-in-ischemic-and-valvular-heart-diseases-and-influenced-by-beta-blockers
#4
Melissa Kristocheck, Lucinara D Dias, Carine Ghem, Bruna Eibel, Renato A K Kalil, Melissa M Markoski
BACKGROUND: Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases...
May 21, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29782989/nadph-oxidase-2-deletion-enhances-neurogenesis-following-traumatic-brain-injury
#5
Jing Wang, Merry W Ma, Krishnan M Dhandapani, Darrell W Brann
The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions...
May 18, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29782191/lipid-protein-and-microrna-composition-within-mesenchymal-stem-cell-derived-exosomes
#6
Hao Deng, Chun Sun, Yingxin Sun, Huhu Li, Lin Yang, Danbin Wu, Qing Gao, Xijuan Jiang
Mesenchymal stem cells (MSCs) were regarded as one of the most promising type of seed cells in tissue engineering due to its easy accessibility and multipotent feature of being able to differentiate into adipocyte, osteoblast, cardiomyocytes, and neurons. For years, MSCs have been applied in treating cardiovascular disease, reconstructing kidney injury, and remodeling immune system with remarkable achievements. Basic researches revealed that its clinic effects are not only due to their pluripotent ability but also through their paracrine function that they synthesize and secrete a broad spectrum of growth factors and cytokines...
May 21, 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29781578/identification-of-an-anti-inflammation-protein-annexin-a1-in-tendon-derived-stem-cells-tdscs-of-cystic-fibrosis-mice-a-comparative-proteomic-analysis
#7
Yang Liu, Lu Feng, Hua Wang, Yu-Jia Wang, Hsiao-Chang Chan, Xiao-Hua Jiang, Wei-Ming Fu, Gang Li, Jin-Fang Zhang
PURPOSE: Our previous study reported an elevated inflammation during tendon injury in mice with cystic fibrosis (CF), indicating the inadequate management of inflammation due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). The objective of this study is to identify the targets of CFTR that contribute to the abnormal inflammation during tendon injury. EXPERIMENTAL DESIGN: A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics was performed to find the molecular targets of CFTR...
May 21, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29780805/stabilization-of-hypoxia-inducible-factor-1-alpha-augments-the-therapeutic-capacity-of-bone-marrow-derived-mesenchymal-stem-cells-in-experimental-pneumonia
#8
Naveen Gupta, Victor Nizet
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29778801/injury-and-stress-responses-of-adult-neural-crest-derived-cells
#9
REVIEW
Vadims Parfejevs, Ana T Antunes, Lukas Sommer
Multipotent neural crest cells can self-renew and give rise to a plethora of neural and non-neural cell types in the vertebrate embryo. Intriguingly, cells reminiscent of such neural crest stem cells (NCSCs) have also been isolated from various postnatal and adult neural crest (NC)-derived structures. However, it has been debated whether NCSC-like cells in the adult correspond to 'in vitro artefacts' emerging upon isolation or fulfil a physiological role in vivo. Here, we discuss recent findings indicating that in different adult NC derivatives, injury or stress responses induce a NCSC-like state, presumably by reprogramming of differentiated cells such as Schwann cells...
May 17, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29778303/the-physiopathologic-interplay-between-stem-cells-and-tissue-niche-in-muscle-regeneration-and-the-role-of-il-6-on-muscle-homeostasis-and-diseases
#10
Laura Forcina, Carmen Miano, Antonio Musarò
Skeletal muscle is a complex, dynamic tissue characterized by an elevated plasticity. Although the adult muscle is mainly composed of multinucleated fibers with post mitotic nuclei, it retains a remarkable ability to regenerate in response to traumatic events. The regenerative potential of the adult skeletal muscle relies in the activity of satellite cells, mononucleated cells residing within the muscle in intimate association with myofibers. Satellite cells normally remain quiescent in their sublaminar position, sporadically entering the cell cycle to guarantee an efficient cellular turnover, by fusing with pre-existing myofibers, and to maintain the stem cell pool...
May 16, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29776607/differentiation-of-equine-bone-marrow-derived-mesenchymal-stem-cells-increases-the-expression-of-immunogenic-genes
#11
Laura Barrachina, Ana Rosa Remacha, Antonio Romero, Pilar Zaragoza, Francisco José Vázquez, Clementina Rodellar
Mesenchymal stem cells (MSCs) are a promising treatment for equine musculoskeletal injuries because of their ability to regulate the inflammation and to differentiate into other cell types. Since interest in allogeneic therapy is rising, concerns about MSC immunogenicity need to be addressed. Differentiated MSCs from several species increase their expression of immunogenic molecules and induce alloresponses, but equine MSC immunogenic profile after differentiation has not been reported. Therefore, the aim of this study was to assess the gene expression of immunogenic markers in tri-lineage differentiated equine bone marrow derived MSCs (eBM-MSCs)...
June 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29775163/methylprednisolone-inhibits-the-proliferation-of-endogenous-neural-stem-cells-in-nonhuman-primates-with-spinal-cord-injury
#12
Jichao Ye, Yi Qin, Yong Tang, Mengjun Ma, Peng Wang, Lin Huang, Rui Yang, Keng Chen, Chaopeng Chai, Yanfeng Wu, Huiyong Shen
OBJECTIVE The aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (ENSCs) in nonhuman primates with spinal cord injury (SCI). METHODS A total of 14 healthy cynomolgus monkeys ( Macaca fascicularis) (4-5 years of age) were randomly divided into 3 groups: the control group (n = 6), SCI group (n = 6), and methylprednisolone therapy group (n = 2). Only laminectomy was performed in the control animals at T-10. SCI was induced in monkeys using Allen's weight-drop method (50 mm × 50 g) to injure the posterior portion of the spinal cord at T-10...
May 18, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29774991/aggregate-mesenchymal-stem-cell-delivery-ameliorates-the-regenerative-niche-for-muscle-repair
#13
Marissa A Ruehle, Hazel Y Stevens, Aaron M Beedle, Robert E Guldberg, Jarrod A Call
Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease due to the absence of the dystrophin protein from the muscle cell membrane which renders the muscle susceptible to continuous damage. In DMD patients, muscle weakness, together with cycles of degeneration/regeneration and replacement with non-contractile tissue, limit mobility and lifespan. Since the loss of dystrophin result in loss of polarity and a reduction in the number of self-renewing satellite cells, it is postulated that these patients could achieve an improved quality of life if delivered cells could restore satellite cell function...
May 18, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29774506/therapeutic-potential-of-mesenchymal-stem-cell-derived-exosomes-in-the-treatment-of-eye-diseases
#14
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Nebojsa Arsenijevic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases...
May 18, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29773058/non-cardiomyocytes-in-heart-regeneration
#15
Jie Feng, Yandong Li, Yu Nie
Heart failure represents a challenging clinical and public health problem and is associated with significant morbidity and mortality. Mechanistically, loss of cardiomyocytes leads to decompensated ventricular remodeling, which eventually progressed to cardiac failure. Regenerative medicine aimed to supplement functional cardiomyocytes is supposedly a promising approach for the effective treatment of heart failure. Over the past decades, investigations on heart regeneration have revealed the regulating networks of cardiomyocyte proliferation...
May 17, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29772932/recent-advances-in-kartogenin-for-cartilage-regeneration
#16
Gaorui Cai, Wei Liu, Yong He, Jianghong Huang, Li Duan, Jianyi Xiong, Lijun Liu, Daping Wang
Either osteoarthritisor sports-related injuries can lead to cartilage defects,whereas both chondrocyte self-renewal and conventional treatments face limitations. In cartilage regenerative medicine, growth factors are commonly used to induce chondrogenic differentiation of stem cells. However, application of growth factors is confined by some drawbacks. Emerging small molecules are regarded as an alternative for cartilage regeneration. A recently discovered small-molecule compound, kartogenin (KGN), has been proven to be a chondrogenic and chondroprotective agent and is more effective in inducing cartilage regeneration when compared with growth factors...
May 18, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29772841/the-effect-of-human-mesenchymal-stem-cells-derived-from-wharton-s-jelly-in-spinal-cord-injury-treatment-is-dose-dependent-and-can-be-facilitated-by-repeated-application
#17
Petr Krupa, Irena Vackova, Jiri Ruzicka, Kristyna Zaviskova, Jana Dubisova, Zuzana Koci, Karolina Turnovcova, Lucia Machova Urdzikova, Sarka Kubinova, Svatopluk Rehak, Pavla Jendelova
Human mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769669/diverse-mechanisms-for-endogenous-regeneration-and-repair-in-mammalian-organs
#18
REVIEW
James M Wells, Fiona M Watt
Mammalian organs comprise an extraordinary diversity of cell and tissue types. Regenerative organs, such as the skin and gastrointestinal tract, use resident stem cells to maintain tissue function. Organs with a lower cellular turnover, such as the liver and lungs, mostly rely on proliferation of committed progenitor cells. In many organs, injury reveals the plasticity of both resident stem cells and differentiated cells. The ability of resident cells to maintain and repair organs diminishes with age, whereas, paradoxically, the risk of cancer increases...
May 2018: Nature
https://www.readbyqxmd.com/read/29769612/hypothermia-broadens-the-therapeutic-time-window-of-mesenchymal-stem-cell-transplantation-for-severe-neonatal-hypoxic-ischemic-encephalopathy
#19
So Yoon Ahn, Yun Sil Chang, Dong Kyung Sung, Se In Sung, Won Soon Park
Recently, we have demonstrated that concurrent hypothermia and mesenchymal stem cells (MSCs) transplantation synergistically improved severe neonatal hypoxic ischemic encephalopathy (HIE). The current study was designed to determine whether hypothermia could extend the therapeutic time window of MSC transplantation for severe neonatal HIE. To induce HIE, newborn rat pups were exposed to 8% oxygen for 2 h following unilateral carotid artery ligation on postnatal day (P) 7. After approving severe HIE involving >50% of the ipsilateral hemisphere volume, hypothermia (32 °C) for 2 days was started...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769390/cell-transplantation-as-a-method-to-investigate-spinal-cord-regeneration-in-regenerative-and-nonregenerative-xenopus-stages
#20
Emilio E Méndez-Olivos, Juan Larraín
Mammals are not capable of regenerating their central nervous system (CNS); anamniotes, however, can regenerate in response to injury. The mechanisms that explain the different regenerative capabilities include: (i) extrinsic mechanisms that consider the cellular environment and extracellular matrix composition, (ii) intrinsic factors implicating the presence or absence of genetic programs that promote axon regeneration, and (iii) the presence or absence of neural stem and progenitors cells (NSPCs) that allow neurogenesis...
May 16, 2018: Cold Spring Harbor Protocols
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