Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation. Methodology/principal findings: Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates. Conclusion/significance: These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation may provide a valuable solution for further standardizing global hPL production methods, increasing the pool of starting material, and meeting future demand for animal-free supplements in human cell culturing

The Malignant Role of Exosomes as Nanocarriers of Rare RNA Species

Publisher's version (útgefin grein)Nowadays, advancements in the oncology sector regarding diagnosis methods allow us to specifically detect an increased number of cancer patients, some of them in incipient stages. However, one of the main issues consists of the invasive character of most of the diagnosis protocols or complex medical procedures associated with it, that impedes part of the patients to undergo routine checkups. Therefore, in order to increase the number of cancer cases diagnosed in incipient stages, other minimally invasive alternatives must be considered. The current review paper presents the value of rare RNA species isolated from circulatory exosomes as biomarkers of diagnosis, prognosis or even therapeutic intervention. Rare RNAs are most of the time overlooked in current research in favor of the more abundant RNA species like microRNAs. However, their high degree of stability, low variability and, for most of them, conservation across species could shift the interest toward these types of RNAs. Moreover, due to their low abundance, the variation interval in terms of the number of sequences with differential expression between samples from healthy individuals and cancer patients is significantly diminished and probably easier to interpret in a clinical context.This research was funded by three national research grants from the Romanian Government: the first one awarded for Frontiers Research Projects 2018-2022 (grant number PN-III-P4-ID-PCCF-2016-112) to Babes Bolyai University, Cluj-Napoca, in collaboration with the Ion Chiricuta Oncology Institute, Cluj-Napoca; the second one awarded for Young Research Teams 2020-2022 (grant number PN-III-P1-1.1-TE2019-0271) to Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, and the third one awarded for Postdoctoral Research Projects 2020-2022 (grant number PN-III-P1-1.1-PD-2019-0805) to Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca. The APC was funded by an international collaborative grant from the European Economic Space between Romania and Iceland 2020-2022 (grant number 19-COP-0031)."Peer Reviewed

Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadRecently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.School of Doctoral Studies - Iuliu Hatieganu University Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca European Economic Spac

B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMalignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman. Keywords: B lymphocytes; T lymphocytes; lymphocyte inter-talk; malignant lymphomas; tumor microenvironment.Iuliu Hatieganu University, School of Doctoral Studies RomanianMinistry of Research and Innovation, CCCDI-UEFISCDI within PNCDI III European Economic Spac

Paul Petroff as the Prince and Tamara Toumanova as the Queen of the Swans, in Le lac des cygnes, the Original Ballet Russe, Australian tour, His Majesty's Theatre, Melbourne, 1940 [picture] /

From: Le lac des cygnes (Swan lake) : choreographic poem in one act / music by Peter Ilich Tchaikovsky; Inscription: "3P/3".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Performed March and April 1940.; Condition: Poor, silvering.; Choreography after M. Petipa ; scenery and costumes by C. Korovine ; scenery executed by O. Allegri.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.pic-vn4175660. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Surface antigen expression of MSC cultured with 10% FBS, 10% HPLF or 10% HPLO.

<p>Surface antigen expression of MSC cultured with 10% FBS, 10% HPLF or 10% HPLO.</p

Letter to Sir Joseph Banks on scientific and experimental matters. Dublin, undated.

Thanks Banks for his hospitality whilst he was in London. This letter is delivered by Thales, a member of the Irish Academy, whom he recommends to Banks. Dated June 24th

Expression of osteogenic marker genes during osteogenic differentiation of MSC.

<p>Osteogenic differentiation was initiated after MSC expansion in 10% of FBS, HPLF or HPLO. Expression of osteogenic marker genes was evaluated after 7 and 21 days of osteogenic differentiation and is represented with graphs for each gene (A–C, n = 3) and a heat-map (D) where green shades represent lower levels of expression and red shades higher levels of expression. <i>ALP</i> was evenly expressed throughout the differentiation (A,D) while the expression of <i>SPP1</i> increased from day 7 to day 21 (B,D), irrespective of the culture supplements the MSC had previously been exposed to (p≤0.01). Expression of <i>RUNX2</i> decreased from day 7 to day 21 for all cultures (C–D), still expression of <i>RUNX2</i> in cultures originating from HPLO treated MSC was higher at both time-points compared to FBS and also at day 21 for HPLF compared to FBS (p≤0.05). * = p≤0.05, ** = p≤0.01.</p

Mesenchymal stem cell morphology during expansion and differentiation.

<p>MSC were stained with crystal violet after expansion in media containing 10% of FBS, HPLF or HPLO for three passages (A–C). MSC cultured in HPLF or HPLO developed more spindle shaped morphology than cells cultured in FBS, proliferated faster and left circular areas containing no cells between them. Differentiation towards osteoblasts, adipocytes and chondrocytes was initiated after expansion in the three supplements. After 28 days of osteogenic differentiation mineralization in the culture could be visualized with a Von Kossa staining (D–F). Successful adipogenic differentiation was confirmed with Oil red O staining (G–I) and after 28 days of chondrogenic pellet cultures, the pellets were sectioned and stained with toludine blue staining (J–L). Pictures representative of three experiments.</p

Cumulative population doublings of MSC after culture in FBS, HPLF or HPLO.

<p>MSC were cultured in culture media supplemented with 10% of FBS, platelet lysate from fresh platelet concentrates (HPLF) or lysate from expired platelet concentrates (HPLO). Population doubling assay was performed at the end of every passage for a total of six passages (P1–P6, n = 3). MSC cultured in either HPLF or HPLO consistently had higher numbers of population doublings at the end of every passage compared to MSC cultured in FBS. By the end of the sixth passage cumulative population doublings were 13.77±0.77 CPD for HPLO, 12.77±0.12 CPD for HPLF and 9.50±1.14 CPD for FBS supplemented cultures, respectively.</p