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Stem cell and intranasal

Taoufiq Harach, Fabien Jammes, Charles Muller, Nicolas Duthilleul, Victoria Cheatham, Valentin Zufferey, David Cheatham, Yelizaveta A Lukasheva, Theo Lasser, Tristan Bolmont
The impact of human adult ischemia-tolerant mesenchymal stem cells (hMSCs) and factors (stem cell factors) on cerebral amyloid beta (Aβ) pathology was investigated in a mouse model of Alzheimer's disease (AD). To this end, hMSCs were administered intravenously to APPPS1 transgenic mice that normally develop cerebral Aβ. Quantitative reverse transcriptase polymerase chain reaction biodistribution revealed that intravenously delivered hMSCs were readily detected in APPPS1 brains 1 hour following administration, and dropped to negligible levels after 1 week...
March 2017: Neurobiology of Aging
Anna Stokowska, Alison L Atkins, Javier Morán, Tulen Pekny, Linda Bulmer, Michaela C Pascoe, Scott R Barnum, Rick A Wetsel, Jonas A Nilsson, Mike Dragunow, Marcela Pekna
Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice...
December 12, 2016: Brain: a Journal of Neurology
Cindy T van Velthoven, Mark Dzietko, Michael F Wendland, Nikita Derugin, Joel Faustino, Cobi J Heijnen, Donna M Ferriero, Zinaida S Vexler
Cell therapy has emerged as a potential treatment for many neurodegenerative diseases including stroke and neonatal ischemic brain injury. Delayed intranasal administration of mesenchymal stem cells (MSCs) after experimental hypoxia-ischemia and after a transient middle cerebral artery occlusion (tMCAO) in neonatal rats has shown improvement in long-term functional outcomes, but the effects of MSCs on white matter injury (WMI) are insufficiently understood. In this study we used longitudinal T2-weighted (T2W) and diffusion tensor magnetic resonance imaging (MRI) to characterize chronic injury after tMCAO induced in postnatal day 10 (P10) rats and examined the effects of delayed MSC administration on WMI, axonal coverage, and long-term somatosensory function...
May 2017: Journal of Neuroscience Research
Deepthi Alapati, Edward E Morrisey
While our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis and alpha 1 antitrypsin deficiency is extensive, treatment options are lacking. Since the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intra-tracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene editing technology is a promising approach to repair or inactivate disease causing mutations...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
Simon G Royce, Anna M Tominaga, Matthew Shen, Krupesh P Patel, Brooke M Huuskes, Rebecca Lim, Sharon D Ricardo, Chrishan S Samuel
Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. This study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX)...
September 19, 2016: Clinical Science (1979-)
Mahua Dey, Dou Yu, Deepak Kanojia, Gina Li, Madina Sukhanova, Drew A Spencer, Katatzyna C Pituch, Lingjiao Zhang, Yu Han, Atique U Ahmed, Karen S Aboody, Maciej S Lesniak, Irina V Balyasnikova
The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs...
September 13, 2016: Stem Cell Reports
Anuradha Kalani, Pankaj Chaturvedi, Pradip K Kamat, Claudio Maldonado, Philip Bauer, Irving G Joshua, Suresh C Tyagi, Neetu Tyagi
We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo(cur)), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8-10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exo(cur) for 7days. Similarly, two sham groups were made and one group received MESC-exo(cur) treatment...
October 2016: International Journal of Biochemistry & Cell Biology
Yan-Hua Li, Jing-Wen Yu, Jian-Yin Xi, Wen-Bo Yu, Jian-Chun Liu, Qing Wang, Li-Juan Song, Ling Feng, Ya-Ping Yan, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms...
September 2, 2016: Molecular Neurobiology
Zhongqi Li, Diana Oganesyan, Rachael Mooney, Xianfang Rong, Matthew J Christensen, David Shahmanyan, Patrick M Perrigue, Joseph Benetatos, Lusine Tsaturyan, Soraya Aramburo, Alexander J Annala, Yang Lu, Joseph Najbauer, Xiwei Wu, Michael E Barish, David L Brody, Karen S Aboody, Margarita Gutova
Pre-clinical studies indicate that neural stem cells (NSCs) can limit or reverse CNS damage through direct cell replacement, promotion of regeneration, or delivery of therapeutic agents. Immortalized NSC lines are in growing demand due to the inherent limitations of adult patient-derived NSCs, including availability, expandability, potential for genetic modifications, and costs. Here, we describe the generation and characterization of a new human fetal NSC line, immortalized by transduction with L-MYC (LM-NSC008) that in vitro displays both self-renewal and multipotent differentiation into neurons, oligodendrocytes, and astrocytes...
September 13, 2016: Stem Cell Reports
Mohammad K El-Badrawy, Nesrien M Shalabi, Mie A Mohamed, Amany Ragab, Heba Wagih Abdelwahab, Nahla Anber, Mohamed A Sobh, Yomna Khater, Aziza A Abdel Hamid
BACKGROUND: In severe chronic stages of emphysema the only treatment is lung transplantation. SO, an urgent need exists for the development of effective treatments. Stem cells therapy arises as a new therapeutic approach. AIM OF THE WORK: To investigate whether bone marrow mononuclar cells (BMMNCs) can promote lung regeneration and decrease apoptosis in lipopolysaccharide (LPS) induced pulmonary emphysema in C57Bl/6 mice. MATERIAL AND METHODS: 14 weeks old female mice (C57Bl/6), weighing around 25 g were used in this study...
May 30, 2016: International Journal of Stem Cells
Byron Oppliger, Marianne Joerger-Messerli, Martin Mueller, Ursula Reinhart, Philipp Schneider, Daniel V Surbek, Andreina Schoeberlein
Preterm white matter injury (WMI) is an important cause for long-term disability. Stem cell transplantation has been proposed as a novel therapeutic approach. However, intracerebral transplantation is not feasible for clinical purpose in newborns. Intranasal delivery of cells to the brain might be a promising, noninvasive therapeutic approach to restore the damaged brain. Therefore, our goal is to study the remyelinating potential of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) after intranasal delivery...
August 15, 2016: Stem Cells and Development
Berta Rodríguez-Frutos, Laura Otero-Ortega, María Gutiérrez-Fernández, Blanca Fuentes, Jaime Ramos-Cejudo, Exuperio Díez-Tejedor
Cell-based therapy has demonstrated safety and efficacy in experimental animal models of stroke, as well as safety in stroke patients. However, various questions remain regarding the therapeutic window, dosage, route of administration, and the most appropriate cell type and source, as well as mechanisms of action and immune-modulation to optimize treatment based on stem cell therapy. Various delivery routes have been used in experimental stroke models, including intracerebral, intraventricular, subarachnoid, intra-arterial, intraperitoneal, intravenous, and intranasal routes...
October 2016: Translational Stroke Research
Antonella Mangraviti, Stephany Y Tzeng, David Gullotti, Kristen L Kozielski, Jennifer E Kim, Michael Seng, Sara Abbadi, Paula Schiapparelli, Rachel Sarabia-Estrada, Angelo Vescovi, Henry Brem, Alessandro Olivi, Betty Tyler, Jordan J Green, Alfredo Quinones-Hinojosa
There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability...
September 2016: Biomaterials
Peng Jiang, Chen Chen, Xiao-Bo Liu, David E Pleasure, Ying Liu, Wenbin Deng
Astrocytes, once considered passive support cells, are increasingly appreciated as dynamic regulators of neuronal development and function, in part via secreted factors. The extent to which they similarly regulate oligodendrocytes or proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) is less understood. Here, we generated astrocytes from human pluripotent stem cells (hiPSC-Astros) and demonstrated that immature astrocytes, as opposed to mature ones, promote oligodendrogenesis in vitro...
May 10, 2016: Cell Reports
Gabriel R Linares, Chi-Tso Chiu, Lisa Scheuing, Yan Leng, Hsiao-Mei Liao, Dragan Maric, De-Maw Chuang
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice...
July 2016: Experimental Neurology
Megan V Jackson, Thomas J Morrison, Declan F Doherty, Daniel F McAuley, Michael A Matthay, Adrien Kissenpfennig, Cecilia M O'Kane, Anna D Krasnodembskaya
Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia...
August 2016: Stem Cells
Hesham T Ghonim, Sumedh S Shah, John W Thompson, Sudheer Ambekar, Eric C Peterson, Mohamed Samy Elhammady
BACKGROUND: Despite advances in the management of subarachnoid hemorrhage, a considerable proportion of patients are still left with severe and disabling long-term consequences. Unfortunately, there are limited therapeutic options to counteract the sequelae following the initial insult. The role of stem cells has been studied in the treatment of various diseases. The goal of this study was to provide a literature review regarding the potential advantages of stem-cell therapy to counteract or minimize the sequelae of aneurysmal subarachnoid hemorrhage...
January 2016: Journal of Vascular and Interventional Neurology
Anita Sapoznikov, Reut Falach, Ohad Mazor, Ron Alcalay, Yoav Gal, Nehama Seliger, Tamar Sabo, Chanoch Kronman
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication...
November 2015: Toxins
S W Kim, J H Kim, C K Park, T J Kim, S Y Lee, Y K Kim, S S Kwon, C K Rhee, H K Yoon
BACKGROUND: Airway remodelling is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Roflumilast is a selective phosphodiesterase-4 inhibitor that has an anti-inflammatory effect in chronic obstructive pulmonary disease (COPD). OBJECTIVE: The objective of this study was to study the effect of roflumilast on airway inflammation and remodelling in a murine model of chronic asthma...
May 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Giulia Leoni, Marguerite Y Wasowicz, Mario Chan, Cuixiang Meng, Raymond Farley, Steven L Brody, Makoto Inoue, Mamoru Hasegawa, Eric W F W Alton, Uta Griesenbach
A key challenge in pulmonary gene therapy for cystic fibrosis is to provide long-term correction of the genetic defect. This may be achievable by targeting airway epithelial stem/progenitor cells with an integrating vector. Here, we evaluated the ability of a lentiviral vector, derived from the simian immunodeficiency virus and pseudotyped with F and HN envelope proteins from Sendai virus, to transduce progenitor basal cells of the mouse nasal airways. We first transduced basal cell-enriched cultures ex vivo and confirmed efficient transduction of cytokeratin-5 positive cells...
2015: Current Gene Therapy
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