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Nadia Naseer, Saliha Bashir, Noreen Latief, Farzana Latif, Shaheen N Khan, Sheikh Riazuddin
AIM: The aim of the present study is to use human amniotic membrane (HAM) for in vitro chondrogenesis of placenta-derived mesenchymal stem cells (MSCs) and umbilical cord-derived MSCs. MATERIALS & METHODS: MSCs from the placenta and umbilical cord were isolated, characterized by immunophenotyping and after analyzing their rate of proliferation, cytotoxicity and viability, chondrogenesis was performed on plastic adherent surface and on HAM. RESULTS: Successfully isolated and characterized placenta-derived MSCs and umbilical cord-derived MSCs revealed positive expression of MSCs markers CD90, CD73, CD105 and CD49d, while they were negative for CD45...
October 2018: Regenerative Medicine
F Rezaei, T Tiraihi, A Abdanipour, H K Hassoun, T Taheri
Valproic acid (VPA) is an inhibitor of histone deacetylases (HDACs) that can regulate differentiation and proliferation of stem cells by epigenetic mechanisms. We investigated VPA induced histone H3 and H4 acetylation in adipose derived stem cells (ADSCs) transdifferentiated into neuron-like cells (NLCs). Rat ADSCs were transdifferentiated into neural stem cells (NSCs) that had been generated from neurospheres. The NSCs were differentiated into NLCs by induction with different concentrations of VPA at 24, 48 and 72 h...
October 1, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Neus Giménez, Alejandra Martínez-Trillos, Arnau Montraveta, Mónica Lopez-Guerra, Laia Rosich, Ferran Nadeu, Juan G Valero, Marta Aymerich, Laura Magnano, Maria Rozman, Estella Matutes, Julio Delgado, Tycho Bauman, Eva Gine, Marcos González, Miguel Alcoceba, M Jose Terol, Blanca Navarro, Enrique Colado, Angel R Payer, Xose S Puente, Carlos López-Otín, Armando Lopez-Guillermo, Elias Campo, Dolors Colomer, Neus Villamor
Mutations in genes of the RAS-BRAF-MAPK-ERK pathway have not been fully explored in chronic lymphocytic leukemia patients. To provide a better comprehension, we analyzed the clinical and biological characteristics of patients with mutations in this pathway and investigated the in vitro response of primary cells to BRAF and ERK inhibitors. Putative damaging mutations were found in 25 of 452 patients (5.5%). Of those, BRAF was mutated in 9 patients (2.0%), genes upstream of BRAF (KITLG, KIT, PTPN11, GNB1, KRAS and NRAS) were mutated in 12 patients (2...
September 27, 2018: Haematologica
XiaoSan Su, Liu Yang, YanFeng Yin, Jie Huang, Fei Qiao, Yu Fang, Lu Yu, YinYin Wang, KaiHua Zhou, Jun Wang
BACKGROUND: Bone marrow mesenchymal stem cells (BMSC) transfer has been attempted as a therapeutic strategy in experimental lung injury and fibrosis. Reduction of neutrophilic infiltration is one of the mechanisms involved in this effect. However, the mechanisms by which BMSC modulate neutrophil remains unknown. METHODS AND RESULTS: Exposure of mice to bleomycin (BLM) resulted in significant accumulation of cells that express neutrophilic markers Gr-1High CD11b+ Ly-6GHigh F4/80- CD115- CD49d- ...
September 26, 2018: Stem Cell Research & Therapy
Oskar McWilliam, Finn Sellebjerg, Hanne V Marquart, Marina Rode von Essen
The contribution of B cells to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is currently of great interest due to the positive outcomes of treatment with B cell-depleting monoclonal antibodies. In this exploratory study we examined the phenotype and cytokine response of B cells from untreated patients with RRMS and healthy controls. The CNS migration potential of the individual blood B cell subpopulations was evaluated according to the expression of CD49d, ALCAM, CXCR3, and CCR7, and cerebrospinal fluid (CSF) samples were analyzed to establish the phenotype of migrated B cells...
November 15, 2018: Journal of Neuroimmunology
Dimitrios Chanouzas, Michael Sagmeister, Lovesh Dyall, Phoebe Sharp, Lucy Powley, Serena Johal, Jessica Bowen, Peter Nightingale, Charles J Ferro, Matthew D Morgan, Paul Moss, Lorraine Harper
BACKGROUND: Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4+ CD28null T cells is seen mainly in cytomegalovirus (CMV)-seropositive individuals and has been linked to increased cardiovascular disease risk in other conditions. The aims of this study were to phenotype CD4+ CD28null T cells in AAV with respect to their pro-inflammatory capacity and ability to target and damage the endothelium and to investigate their relationship to arterial stiffness, a marker of cardiovascular mortality...
August 29, 2018: Arthritis Research & Therapy
Lisa Borkner, Alicja Misiak, Mieszko M Wilk, Kingston H G Mills
Treatment with the macrolide antibiotic azithromycin (AZM) is an important intervention for controlling infection of children with Bordetella pertussis and as a prophylaxis for preventing transmission to family members. However, antibiotics are known to have immunomodulatory effects independent of their antimicrobial activity. Here, we used a mouse model to examine the effects of AZM treatment on clearance of B. pertussis and induction of innate and adaptive immunity. We found that treatment of mice with AZM either 7 or 14 days post challenge effectively cleared the bacteria from the lungs...
2018: Frontiers in Immunology
Jae-Ghi Lee, Joon Young Jang, Taishi Fang, Yixuan Xu, Ji-Jing Yan, Jung-Hwa Ryu, Hee Jung Jeon, Tai Yeon Koo, Dong Ki Kim, Kook-Hwan Oh, Tae Jin Kim, Jaeseok Yang
Human B-1 cells have been proposed to be CD20+ CD27+ CD43+ CD1c- B cells found in the umbilical cord and adult peripheral blood, but their regulatory mechanisms have not been well elucidated. Previously, we reported that mouse CD49dhigh CD4+ T cells could enhance the secretion of natural antibodies by B-1 cells. In this study, we aimed to investigate the presence and helper functions of the human equivalents of murine CD49dhigh CD4+ T cells. Here, we showed that human CD49dhigh CD4+ T cells found in the peritoneal cavity (PEC), spleen, and peripheral blood can enhance the production of IgM antibodies by B-1 cells...
2018: Frontiers in Immunology
Lisa Lohmann, Claudia Janoschka, Andreas Schulte-Mecklenbeck, Svenja Klinsing, Lucienne Kirstein, Uta Hanning, Timo Wirth, Tilman Schneider-Hohendorf, Nicholas Schwab, Catharina C Gross, Maria Eveslage, Sven G Meuth, Heinz Wiendl, Luisa Klotz
Leukocyte sequestration is an established therapeutic concept in multiple sclerosis (MS) as represented by the trafficking drugs natalizumab (NAT) and fingolimod (FTY). However, the precise consequences of targeting immune cell trafficking for immunoregulatory network functions are only incompletely understood. In the present study, we performed an in-depth longitudinal characterization of functional and phenotypic immune signatures in peripheral blood (PB) and cerebrospinal fluid (CSF) of 15 MS patients during switching from long-term NAT to FTY treatment after a defined 8-week washout period within a clinical trial (ToFingo successor study; ClinicalTrials...
2018: Frontiers in Immunology
Richard Thomson-Luque, Chengqi Wang, Francis B Ntumngia, Shulin Xu, Karoly Szekeres, Amy Conway, Swamy Rakesh Adapa, Samantha J Barnes, John H Adams, Rays H Y Jiang
Progress towards an in-depth understanding of the final steps of the erythroid lineage development is paramount for many hematological diseases. We have characterized the final stages of reticulocyte maturation from bone marrow to peripheral blood using for the first time single-cell Mass Cytometry (CyTOF). We were able to measure the expression of 31 surface markers within a single red blood cell (RBC). We demonstrate the validity of CyTOF for RBC phenotyping by confirming the progressive reduction of transferrin receptor 1 (CD71) during reticulocyte maturation to mature RBC...
September 2018: Blood Cells, Molecules & Diseases
Kyle Crassini, Yandong Shen, Michael O'Dwyer, Michael O'Neill, Richard Christopherson, Stephen Mulligan, O Giles Best
Despite significant advances in treatment, chronic lymphocytic leukaemia (CLL) remains an incurable disease. Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-δ respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway. IBL-202 is a dual inhibitor of the PIM and PI3 kinases. Synergy between the pan-PIM inhibitor, pPIMi, and idelalisib against a range of haematological cell lines and primary CLL cells supports the rationale for preclinical studies of IBL-202 in CLL...
September 2018: British Journal of Haematology
Jaeyeon Choi, Wissam Beaino, Ronald Fecek, Kellsye Fabian, Charles M Laymon, Brenda Kurland, Walter Storkus, Carolyn J Anderson
Very late antigen-4 (VLA-4; also known as integrin α4β1) is expressed at high levels in aggressive and metastatic melanoma tumors and may provide an ideal target for imaging and targeted radiotherapy. 177 Lu-DOTA-PEG4-LLP2A (177 Lu-LLP2A) shows high affinity for VLA-4 and had high uptake in B16F10 mouse melanoma tumors in vivo. Here, we report efficacy studies of 177 Lu-LLP2A, alone and combined with immune checkpoint inhibitors (ICI) in B16F10 tumor-bearing mice. Methods: B16F10 tumor cells (1 x 106) were implanted subcutaneously in C57BL/6 mice...
June 29, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Csilla Kriston, Márk Plander, Ágnes Márk, Anna Sebestyén, Edina Bugyik, András Matolcsy, Gábor Barna
CD49d and CXCR4 are key determinants of interactions between chronic lymphocytic leukemia (CLL) tumor cells and their microenvironment. In this study, we investigated the effect of CD49d and CXCR4 expressions on survival of CLL cells. Primary CLL cells were cultured with CD49d ligand, VCAM-1, or bone marrow stromal cells (BMSCs); then, apoptosis and immunophenotype analyses were performed. VCAM-1 treatment could not induce direct apoptosis protection or immunophenotype change on the CD49d-expressing CLL cells, but resulted in actin reorganization...
November 2018: Annals of Hematology
Samih Mohamed-Ahmed, Inge Fristad, Stein Atle Lie, Salwa Suliman, Kamal Mustafa, Hallvard Vindenes, Shaza B Idris
BACKGROUND: Adipose-derived stem cells (ASCs) have been introduced as an alternative to bone marrow mesenchymal stem cells (BMSCs) for cell-based therapy. However, different studies comparing ASCs and BMSCs have shown conflicting results. In fact, harvesting ASCs and BMSCs from different individuals might influence the results, making comparison difficult. Therefore, this study aimed to characterize donor-matched ASCs and BMSCs in order to investigate proliferation, differentiation potential and possible effects of donor variation on these mesenchymal stem cells (MSCs)...
June 19, 2018: Stem Cell Research & Therapy
Anjali Chauhan, Jacob Hudobenko, Abdullah Al Mamun, Edward C Koellhoffer, Anthony Patrizz, Rodney M Ritzel, Bhanu P Ganesh, Louise D McCullough
BACKGROUND: Activation of transforming growth factor-β-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury...
May 17, 2018: Journal of Neuroinflammation
Zhi-Jie Liang, Xiang Lu, De-Quan Li, Yi-Dan Liang, Dan-Dan Zhu, Fang-Xiao Wu, Xiao-Lin Yi, Ning He, Yan-Qing Huang, Chao Tang, Hong-Mian Li
BACKGROUND/AIMS: The rejuvenation properties of nanofat grafting have been described in recent years. However, it is not clear whether the clinical efficacy of the procedure is attributable to stem cells or linked to other components of adipose tissue. In this study we isolated nanofat-derived stem cells (NFSCs) to observe their biological characteristics and evaluate the efficacy of precise intradermal injection of nanofat combined with platelet-rich fibrin (PRF) in patients undergoing facial rejuvenation treatment...
2018: Cellular Physiology and Biochemistry
Francesco Autore, Paolo Strati, Luca Laurenti, Alessandra Ferrajoli
Chronic lymphocytic leukemia is an extremely heterogeneous disease and prognostic factors such as chromosomal abnormalities are important predictors of time to first treatment and survival. Trisomy 12 is the second most frequent aberration detected by fluorescence in situ hybridization at the time of diagnosis (10-25%), and it confers an intermediate prognostic risk, with a median time to first treatment of 33 months and a median overall survival of 114 months. Here, we review the unique morphological, immunophenotypic, and genetic characteristics of patients with chronic lymphocytic leukemia and trisomy 12...
June 2018: Haematologica
Lauren A Thurgood, Karen M Lower, Cindy Macardle, Bryone J Kuss
The cryopreservation of peripheral blood mononuclear cells (PBMCs) is a routine research laboratory process, enabling long-term storage of primary patient blood samples. Retrospective analysis of these samples has the potential to identify markers that may be associated with prognosis and response to treatment. To draw valid biological conclusions from this type of analysis, it is essential to ensure that any observed changes are directly related to the pathology of the disease rather than the preservation process itself...
July 2018: Experimental Hematology
Peter Herbener, Kurt Schönfeld, Martin König, Matthias Germer, Jude M Przyborski, Katrin Bernöster, Jörg Schüttrumpf
An increasing number of monoclonal antibodies and derivatives such as antibody-drug conjugates (ADC) are of the IgG1 and IgG4 isotype with distinct structural and functional properties. In cases where antibody-mediated cytotoxicity is not desired, IgG4 is often used, as its Fc region is relatively poor at inducing antibody-dependent cell-mediated or complement-dependent cytotoxicity. IgG4 ADCs with highly cytotoxic drugs against proliferating target cells but which lack or have diminished antibody effector functions against quiescent cells may have a favorable safety profile compared to IgG1...
2018: PloS One
Nalinikanth Kotagiri, Matthew L Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F DiPersio, Samuel Achilefu
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells...
January 18, 2018: Nature Communications
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