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Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Alberto L Horenstein, Valeria Quarona, Denise Toscani, Federica Costa, Antonella Chillemi, Vito Pistoia, Nicola Giuliani, Fabio Malavasi
Human myeloma cells express CD38 at high levels and grow in hypoxic niches inside the bone marrow. Myeloma cells respond to hypoxia with metabolic changes leading to aerobic glycolysis, thus reducing ATP and increasing NAD(+). Our hypothesis is that these conditions favor the enzymatic pathways involved in the production of adenosine in the niche. Within the niche, NAD(+) is able to activate a discontinuous adenosinergic pathway that relies upon CD38, CD203a, and CD73 or TRACP, according to the environmental pH...
October 13, 2016: Molecular Medicine
Alexandra Condé-Green, Vasanth S Kotamarti, Lauren S Sherman, Jonathan D Keith, Edward S Lee, Mark S Granick, Pranela Rameshwar
: Standard isolation of adipose stromal vascular fraction (SVF) requires the use of collagenase and is considered more than "minimally manipulated" by current good manufacturing practice requirements. Alternatively, nonenzymatic isolation methods have surfaced using physical forces to separate cells from the adipose matrix. The purpose of this study was to review the literature on the use of mechanical isolation protocols and compare the results. The implication for use as a standard procedure in practice is discussed...
September 2016: Plastic and Reconstructive Surgery. Global Open
Luca Antonioli, Corrado Blandizzi, Fabio Malavasi, Davide Ferrari, György Haskó
The ecto-5'-nucleotidase/CD73 enzyme plays a pivotal role in generating an adenosine-enriched immunosuppressed and pro-angiogenic niche supporting cancer development. The targeting of CD73 leads to reorganization of tumor microenvironment, shaping the phenotype of the infiltrating T cells. The development of CD73 monoclonal antibodies offers a promising new avenue for antineoplastic treatment.
2016: Oncoimmunology
Anna Otte, Yuanyuan Yang, Juliane von der Ohe, Catharina Melzer, Peter Hillemanns, Friedrich Feuerhake, Ralf Hass
Chemotherapeutic drug testing of SCCOHT-1 and BIN-67 tumor cells revealed synergistic growth-inhibition of >95% in vitro with a combination of foretinib and FK228. Application of this drug combination in vivo in NODscid mice-induced SCCOHT-1GFP tumors was associated with ~6-fold reduction in tumor mass within 10 days, whereby synergistic effects of the two compounds remained undetectable compared to previous results with foretinib treatment alone. Histopathologic evaluation revealed a reduced vascularization and a lower amount of proliferating cells in the treated tumors...
October 14, 2016: International Journal of Oncology
Francesco De Francesco, Antonio Graziano, Letizia Trovato, Gabriele Ceccarelli, Maurizio Romano, Marco Marcarelli, Gabriella Maria Casella De Angelis, Umberto Cillo, Michele Riccio, Giuseppe Andrea Ferraro
BACKGROUND: The etiology of non-healing ulcers depends on both systemic and local factors. The introduction of advanced dressing, negative wound therapy and compression therapy have undoubtedly improved clinical outcomes. The principal aim of study was to demonstrate the efficacy of dermal micrografts in the treatment of ulcers with different etiologies. The second aim was to investigate in vitro the action of micrografts in the regenerative process. METHODS: The dermal micro-grafts were obtained from mechanical disaggregation of small pieces of skin tissue through a medical device called Rigeneracons...
October 13, 2016: Stem Cell Reviews
Shuang Zhang, Chunyu Bai, Dong Zheng, Yuhua Gao, Yanan Fan, Lu Li, Weijun Guan, Yuehui Ma
Adipose-derived stem cells (ADSCs) are multipotent, and can be differentiated into many cell types in vitro. In this study, tissues from pigs were chosen to identify and characterize ADSCs. Primary ADSCs were sub-cultured to passage 28. The surface markers of ADSCs: CD29, CD71, CD73, CD90, and CD166 were detected by reverse-transcription polymerase chain reaction assays and the markers CD29, CD44, CD105, and vimentin were detected by immunofluorescence. Growth curves and the capacity of clone-forming were performed to test the proliferation of ADSCs...
October 2016: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
Suvi T Vaara, Maija Hollmén, Anna-Maija Korhonen, Mikael Maksimow, Tero Ala-Kokko, Marko Salmi, Sirpa Jalkanen, Ville Pettilä
BACKGROUND: CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality. METHODS: This was a post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011-2012...
2016: PloS One
Jezamine Lim, Zainul Rashid Mohamad Razi, Jiaxian Law, Azmawati Mohammed Nawi, Ruszymah Binti Haji Idrus, Min Hwei Ng
BACKGROUND AIMS: Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied...
October 7, 2016: Cytotherapy
Zala Lužnik, Marko Hawlina, Elvira Maličev, Marina Bertolin, Andreja Nataša Kopitar, Alojz Ihan, Stefano Ferrari, Petra Schollmayer
PURPOSE: To evaluate the effect of prolonged limbal explants cultured without any scaffolds or on amniotic membrane (AM) on the viability, proliferation and differentiation potential of putative phenotypically defined cultured limbal mesenchymal (LMSC) and epithelial stem cells (LESC). METHODS: Limbal explants were cultivated on cryopreserved intact AM or plastic plates using medium supplemented with only human serum. AM was positioned with either the epithelial or stromal side up...
2016: PloS One
Prashant R Tembhare, Sitaram Ghogale, Nisha Ghatwai, Yajamanam Badrinath, Nikesh Kunder, Nikhil V Patkar, Asma R Bibi, Gaurav Chatterjee, Brijesh Arora, Gaurav Narula, Shripad Banawali, Nilesh Deshpande, Prathibha Amare, Sumeet Gujral, Papagudi G Subramanian
BACKGROUND: Multiparametric flow cytometry (MFC) is a popular technique for minimal residual disease (MRD) analysis. However, its applicability is still limited to 90% of B-cell precursor acute lymphoblastic leukemia (BCPALL) due to two major issues, i.e. a proportion of cases do not express adequate leukemia associated immunophenotype (LAIPs) with currently used markers and drug-induced antigen-modulation. Hence, the incorporation of additional reliable markers is required for the further improvement of MFC-based MRD evaluation...
October 7, 2016: Cytometry. Part B, Clinical Cytometry
Deng Pan, Somdutta Roy, Philippe Gascard, Jianxin Zhao, Chira Chen-Tanyolac, Thea D Tlsty
Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit extensive lineage plasticity in vitro and in vivo. Here we visualize these rare ePS cells in a latent state, i.e. lacking SOX2, OCT3/4 and NANOG (SON) expression, in non-diseased breast specimens through immunohistochemical analysis of previously identified ePS-specific biomarkers (CD73(+), EpCAM(+) and CD90(-)). We also report a novel mechanism by which these latent ePS cells acquire SON expression and plasticity in vitro. Four extracellular factors are necessary for the acquisition of SON expression and lineage plasticity in ePS cells: adenosine (which is produced by the 5' ecto-nucleotidase CD73 and activates in turn the PKA-dependent IL6/STAT3 pathway through the adenosine receptor ADORA2b), IL6, FGF2 and ACTIVIN A...
December 2016: Cellular Signalling
Anna M Knapinska, Sabrina Amar, Zhong He, Sandro Matosevic, Claudia Zylberberg, Gregg B Fields
Cell isolation methods for therapeutic purposes have seen little advancement over the years. The original methods of stem cell and islet isolation using bacterial collagenases were developed in the early 1980s and are still used today. Bacterial collagenases are subject to autodegradation, and isolates obtained with these enzymes may be contaminated with endotoxins, reducing cell viability and contributing to toxicity in downstream applications. Here we describe a novel method for isolation of mesenchymal stem cells from adipose tissue (ADSC) utilizing recombinantly produced matrix metalloproteases (MMPs)...
November 2016: Enzyme and Microbial Technology
Dongchun Liang, Aijun Zuo, Ronglan Zhao, Hui Shao, Willi K Born, Rebecca L O'Brien, Henry J Kaplan, Deming Sun
[This corrects the article DOI: 10.1371/journal.pone.0150078.].
2016: PloS One
O G Davies, L M Grover, M P Lewis, Y Liu
Heterotopic ossification (HO) is a debilitating condition defined by the rapid formation of bone in soft tissues. What makes HO fascinating is firstly the rate at which bone is deposited, and secondly the fact that this bone is structurally and compositionally similar to that of a healthy adult. If the mechanisms governing HO are understood, they have the potential to be exploited for the development of potent osteoinductive therapies. With this aim, we utilised a tissue engineered skeletal muscle model to better understand the role of inflammation on this debilitating phenomenon...
October 3, 2016: Journal of Tissue Engineering and Regenerative Medicine
(no author information available yet)
Cotargeting CD73 and A2AR overcomes host-ablated A2AR-induced CD73 expression.
September 30, 2016: Cancer Discovery
Alessandra Giorgetti, Julio Castaño, Clara Bueno, Rafael Diaz de la Guardia, Mario Delgado, Anna Bigas, Lluis Espinosa, Pablo Menendez
Recent studies in zebrafish and mice demonstrated that proinflammatory signaling is a positive regulator of definitive hematopoietic development. Whether proinflammatory signaling regulates also human hematopoietic specification remains unknown. Here, we explored the impact of the proinflammatory cytokines tumor necrosis factor-α (TNFα), interferon-γ (IFNγ) and interleukin-1β (IL1β) on in vitro hematopoietic differentiation using human pluripotent stem cells (hPSCs). Gene expression analysis and ELISA revealed the absence of a proinflammatory signature during hematopoietic development of hPSCs...
September 27, 2016: Experimental Hematology
Laura E Sidney, Andrew Hopkinson
Keratocytes of the corneal limbal stroma can derive populations of mesenchymal stem cells (MSC) when expanded in vitro. However, once a corneal MSC (cMSC) phenotype is achieved, regaining the keratocyte phenotype can be challenging, and there is no standardised differentiation medium. Here, we investigated the transition of keratocytes to cMSC and compared different supplements in their ability to return cMSC to a keratocyte phenotype. Immunofluorescence and RT-qPCR demonstrated in vivo keratocyte expression of ALDH3A1, CD34 and keratocan, but not any of the typical MSC markers (CD73, CD90, CD105)...
September 29, 2016: Journal of Tissue Engineering and Regenerative Medicine
Tereza C Cardoso, Lucas H Okamura, Jamila C Baptistella, Roberto Gameiro, Helena L Ferreira, Márcia Marinho, Eduardo F Flores
The possibility of isolating bovine mesenchymal multipotent stromal cells (MSCs) from fetal adnexa is an interesting prospect due to the potential use of these cells in biotechnological applications. However, little is known about the properties of these progenitor cells in bovine species. Wharton's jelly (WJ) MSC cells were obtained from the umbilical cord of bovine fetuses at three different stages of pregnancy and divided into groups 1, 2 and 3 according to gestational trimester. Cell morphology, from the three stages of pregnancy, typically appeared fibroblast-like spindle-shaped, presenting the same viability and number...
September 27, 2016: Cell and Tissue Research
Mohammad-Ali Jenabian, Cecilia T Costiniuk, Vikram Mehraj, Feras M Ghazawi, Rémi Fromentin, Joëlle Brousseau, Pierre Brassard, Maud Bélanger, Petronela Ancuta, Reina Bendayan, Nicolas Chomont, Jean-Pierre Routy
OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically-privileged compartment. We assessed immuno-tolerance properties of the testicular tissue in individuals receiving suppressive ART. DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from 6 virally suppressed adults and 10 HIV-uninfected controls prior to gender reassignment surgery...
September 24, 2016: AIDS
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