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cellular transplantation

Mei-Le Keck, Florian Wrensch, Brian G Pierce, Thomas F Baumert, Steven K H Foung
Hepatitis C virus (HCV) continues to spread worldwide with an annual increase of 1.75 million new infections. The number of HCV cases in the U.S. is now greater than the number of HIV cases and is increasing in young adults because of the opioid epidemic sweeping the country. HCV-related liver disease is the leading indication of liver transplantation. An effective vaccine is of paramount importance to control and prevent HCV infection. While this vaccine will need to induce both cellular and humoral immunity, this review is focused on the required antibody responses...
2018: Frontiers in Immunology
Andi Wang, Hua Zhong
OBJECTIVES: To summarize the effects of the bone marrow niche on hematopoiesis and leukemogenesis and discuss the chemotherapy resistance that can arise from interactions between the niche and leukemia stem cells. METHODS: We review the major roles of the bone marrow niche in cell proliferation, adhesion and drug resistance. The signaling pathways and major molecular participants in the niche are discussed. We also address potential niche-targeting strategies for the treatment of acute myeloid leukemia (AML)...
June 14, 2018: Hematology (Amsterdam, Netherlands)
R J Arasaratnam, I Tzannou, T Gray, P I Aguayo-Hiraldo, M Kuvalekar, S Naik, A Gaikwad, H Liu, T Miloh, J F Vera, R W Himes, F M Munoz, A M Leen
Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between post-transplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year post-transplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered post-transplant, coincident with the introduction and subsequent routine tapering of immunosuppression...
June 13, 2018: American Journal of Transplantation
Carlos Solano, Estela Giménez, Eliseo Albert, Eva María Mateo, Montserrat Gómez, Rosa Goterris, Ariadna Pérez, Paula Amat, Juan Carlos Hernández-Boluda, Marc Poch, José Luis Piñana, David Navarro
To gauge the risk of delaying initiation of prophylaxis with letermovir from the time of donor infusion to prevent CMV infection in allo-HSCT recipients we investigated the clinical outcomes of CMV DNAemia episodes occurring before engraftment, and compared to that of episodes developing after engraftment (up to day +365). A total of 197 consecutive adult patients were included. Plasma CMV DNA load was monitored by real-time PCR assays [limit of detection: 31 IU/ml]. A total of 150 out of 197 patients had CMV DNAemia (cumulative incidence of 77%; 95% CI, 73-81%), and 38 out of the 197 patients developed it before engraftment (cumulative incidence, 19%; 95% CI, 10-30...
June 13, 2018: Bone Marrow Transplantation
Beata Greb-Markiewicz, Mirosław Zarębski, Andrzej Ożyhar
Neuronal Per-Arnt-Sim (PAS) domain-containing protein 4 (NPAS4) is a basic helix-loop-helix (bHLH)-PAS transcription factor that was first discovered in neurons in the neuronal layer of the mammalian hippocampus and was later discovered in pancreatic β-cells. NPAS4 has been proposed as a therapeutic target not only for depression and neurodegenerative diseases associated with synaptic dysfunction but also for type 2 diabetes and pancreas transplantation. The ability of bHLH-PAS proteins to fulfil their function depends on their intracellular trafficking, which is regulated by specific sequences, i...
June 13, 2018: Journal of Biological Chemistry
Ryuta Koyama, Yuji Ikegaya
The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully) supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain...
2018: Frontiers in Neurology
Carola Ledderose, Kaifeng Liu, Yutaka Kondo, Christian J Slubowski, Thomas Dertnig, Sara Denicoló, Mona Arbab, Johannes Hubner, Kirstin Konrad, Mahtab Fakhari, James A Lederer, Simon C Robson, Gary A Visner, Wolfgang G Junger
T cells must migrate in order to encounter antigen-presenting cells (APCs) and to execute their varied functions in immune defense and inflammation. ATP release and autocrine signaling through purinergic receptors contribute to T cell activation at the immune synapse that T cells form with APCs. Here, we show that T cells also require ATP release and purinergic signaling for their migration to APCs. We found that the chemokine SDF-1α triggered mitochondrial ATP production, rapid bursts of ATP release, and increased migration of primary human CD4+ T cells...
June 12, 2018: Journal of Clinical Investigation
Clarissa Hernandez Stephens, Kara S Orr, Anthony J Acton, Sarah A Tersey, Raghavendra G Mirmira, Robert V Considine, Sherry L Voytik-Harbin
Widespread use of pancreatic islet transplantation for treatment of type 1 diabetes (T1D) is currently limited by requirements for long-term immunosuppression, limited donor supply, and poor long-term engraftment and function. Upon isolation from their native microenvironment, islets undergo rapid apoptosis, which is further exacerbated by poor oxygen and nutrient supply following infusion into the portal vein. Identifying alternative strategies to restore critical microenvironmental cues, while maximizing islet health and function, are needed to advance this cellular therapy...
June 12, 2018: American Journal of Physiology. Endocrinology and Metabolism
Narendra S Choudhary, Sanjiv Saigal, Neeraj Saraf, Amit Rastogi, Sanjay Goja, Prashant Bhangui, Srinivasan Thiagrajan, Dheeraj Gautam, Deepak Govil, Vijay Vohra, Arvinder S Soin
Introduction: Although liver transplantation is a definitive cure for Wilson's disease (WD), there is limited data about results of living donor liver transplantation (LDLT) in adults. Material and methods: 18 adults underwent LDLT for WD. The presentations before LDLT were decompensated cirrhosis ( n  = 16), acute on chronic liver failure ( n  = 1) and acute liver failure ( n  = 1). The donors were parents ( n  = 2), siblings ( n  = 3), cousin ( n  = 1), daughter ( n  = 1), nephew ( n  = 1), spouse or relatives of spouse ( n  = 9) and from swap transplantation ( n  = 1)...
June 2018: Journal of Clinical and Experimental Hepatology
Stephen Polgar, Leila Karimi, Melissa Buultjens, Meg E Morris, Monica Busse
Evidence from a growing number of preclinical studies indicate that recently discovered stem cell lines may be translated into viable cellular therapies for people with Parkinson's disease. In a brief but critical review, we examine the use of primary and secondary outcome measures currently used to evaluate the efficacy of cellular therapies. The current practice of relying on a single primary outcome measure does not appear to provide the evidence required for demonstrating the robust, life-changing recovery anticipated with the successful implementation of cellular therapies...
June 5, 2018: Journal of Parkinson's Disease
Ashraf Omar, Pradnya D Patil, Sami Hoshi, Jasmine Huang, Earle Collum, Tanmay S Panchabhai
A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18 months prior. His posttransplant course was fairly unremarkable until 1 month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening...
June 2018: Chest
Zhe Jia, Fei Li, Xiaoyu Zeng, Ying Lv, Shaozhen Zhao
BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to promote long-term cellular and organ transplant acceptance due to their immunotherapeutic characteristics. Previous work from our lab using a rat allograft model has shown that systemic infusion of MSCs inhibited corneal allograft rejection and prolonged graft survival. Here, we further investigated the effects of local MSCs administration in the same animal model. METHODS: Donor-derived MSCs were isolated and cultured while corneal grafts obtained from Wistar rats were transplanted into Lewis rat hosts...
June 8, 2018: BMC Ophthalmology
Joao Paulo Zambon, In Kap Ko, Mehran Abolbashari, Jennifer Huling, Cara Clouse, Tae Hyoung Kim, Charesa Smith, Anthony Atala, James J Yoo
Kidney transplantation is currently the only definitive solution for the treatment of end-stage renal disease (ESRD), however transplantation is severely limited by the shortage of available donor kidneys. Recent progress in whole organ engineering based on decellularization/recellularization techniques has enabled pre-clinical in vivo studies using small animal models; however, these in vivo studies have been limited to short-term assessments. We previously developed a decellularization system that effectively removes cellular components from porcine kidneys...
June 5, 2018: Acta Biomaterialia
Shiva Pathak, Shobha Regmi, Tiep Tien Nguyen, Biki Gupta, Milan Gautam, Chul Soon Yong, Jong Oh Kim, Youlim Son, Jae-Ryong Kim, Min Hui Park, Young Kyung Bae, So Young Park, Daewon Jeong, Simmyung Yook, Jee-Heon Jeong
Attenuation of senescence progression may be attractive way to preserve the functionality of pancreatic islets (PI) after transplantation. In this study, we developed a model for in vitro induction of premature senescence in rat PI and showed the effectiveness of quercetin (QU) to prevent the senescence. To provide targeted-delivery of QU to the PI after transplantation, we prepared the hybrid clusters (HC) of islet single cells (ISC) and QU-loaded polymeric microspheres (QU; ∼7.55 ng HC-1 ). Long-term culture of the HC revealed reduced levels of reactive oxygen species and decreased expression of senescence-associated beta galactosidase, Rb, p53, p16, and p21 compared to that of the control islets...
June 5, 2018: Acta Biomaterialia
Fabio Baroni, Chiara Marraccini, Lucia Merolle, Vando Piccagli, Daniele Lambertini, Mauro Iori, Tommaso Fasano, Emanuela Casali, Alberto Spisni, Roberto Baricchi, Thelma A Pertinhez
The upholding of red blood cells (RBC) quality and the removal of leukocytes are two essential issues in transfusion therapy. Leukodepletion provides optimum results, nonetheless there are cases where irradiation is recommended for some groups of hematological patients such as the ones with chronic graft-vs-host disease, congenital cellular immunodeficiency, and hematopoietic stem cell transplant recipients. The European guidelines suggest irradiation doses from 25 to 50 Gray (Gγ). We evaluated the effect of different prescribed doses (15 to 50 Gγ) of X-ray irradiation on fresh leukodepleted RBCs bags using a novel protocol that provides a controlled irradiation...
June 7, 2018: Annals of Hematology
BaoHan T Vo, Jin Ah Kwon, Chunliang Li, David Finkelstein, Beisi Xu, Brent A Orr, Charles J Sherr, Martine F Roussel
MYC-driven Group 3 (G3) medulloblastoma (MB) is the most aggressive of four molecular subgroups classified by transcriptome, genomic landscape and clinical outcomes. Mouse models that recapitulate human G3 MB all rely on retroviral vector-induced Myc expression driven by viral regulatory elements (Retro-Myc tumors). We used nuclease-deficient CRISPR/dCas9-based gene activation with combinatorial single guide RNAs (sgRNAs) to enforce transcription of endogenous Myc in Trp53-null neurospheres that were orthotopically transplanted into the brains of naïve animals...
June 7, 2018: Scientific Reports
E A Lendermon, J M Dodd-O, T A Coon, X Wang, C R Ensor, N Cardenes, C L Koodray, H L Heusey, M F Bennewitz, P Sundd, G C Bullock, I Popescu, L Guo, C P O'Donnell, M Rojas, J F McDyer
BACKGROUND: Cellular and molecular mechanisms of acute and chronic lung allograft rejection have yet to be clearly defined, and obliterative bronchiolitis (OB) remains the primary limitation to survival in lung transplant recipients (LTRs). We have previously shown that T-bet-deficient recipients of full major histocompatibility complex (MHC)-mismatched, orthotopic left lung transplants develop accelerated obliterative airway disease (OAD) in the setting of acute cellular rejection characterized by robust alloimmune CD8+ interleukin (IL)-17 and interferon (IFN)-γ responses that are attenuated with neutralization of IL-17...
June 2018: Transplantation Proceedings
X-F Zou, B Song, J-H Duan, Z-D Hu, Z-L Cui, T Yang
BACKGROUND: Previously, high levels of CXCR3+ T-cell recruitment was demonstrated in the prolonged ischemia-accelerated acute allograft rejection in rat kidney transplant. In the present study, the effect of chemokine IP-10 was investigated and the expression of chemokine-related PRINS (Psoriasis susceptibility-related RNA gene induced by stress) lncRNA determined in the allografts subjected to ischemia. METHODS: F344-to-Lewis rat kidney transplantation was performed, and renal grafts were stored for 2 hours or 16 hours...
June 2018: Transplantation Proceedings
J H Kwon, I A Hanouneh, D Allende, L Yerian, T Diago, B Eghtesad, N N Zein
INTRODUCTION: De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. METHODS: Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies...
June 2018: Transplantation Proceedings
Y K Son, H Kwon, H W Lee, E G Jeong, S M Lee, S E Kim, Y Park, W S An
BACKGROUND: Modifications of erythrocyte membrane fatty acid (FA) contents may affect cellular function or transmembrane receptors. One cross-sectional study has shown that kidney transplant (KTP) recipients have lower erythrocyte membrane oleic acid content than dialysis patients do. Therefore, we prospectively tested whether erythrocyte membrane contents of FA including oleic acid change after KTP. METHODS: We recruited 23 KTP recipients (September 2011 through May 2014)...
June 2018: Transplantation Proceedings
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