Heparin Differentially Regulates the Expression of Specific miRNAs in Mesenchymal Stromal Cells.

In regenerative medicine, stromal cells are supposed to play an important role by modulating immune responses and differentiating into various tissue types. The aim of this study was to investigate the influence of heparin, frequently used as an anticoagulant in human platelet lysate (HPL)-supplemented cell cultures, on the expression of non-coding RNA species, particularly microRNAs (miRNA), which are pivotal regulators of gene expression. Through genomic analysis and quantitative RT-PCR, we assessed the differential impact of heparin on miRNA expression in various stromal cell types, derived from human bone marrow, umbilical cord and white adipose tissue.

Evaluating a New Photopheresis System: A Comparison with Two Established Systems on Cell Yield and Collection Efficiency.

Unlabelled: : Extracorporeal photopheresis (ECP) is a well-established and efficacious cell therapy for a range of diseases. The objective of this retrospective study was to compare the new Amicus Blue inline system with the Therakos Cellex inline system and the Spectra Optia offline system in terms of collection efficiency, mononuclear cell (MNC) yield of mononuclear cell products (MCPs), processing time and correlation between MCP cell count and peripheral blood count of patients.

Methods: This retrospective study compared 127 procedures utilizing the Spectra Optia offline system, 93 procedures employing the Amicus Blue inline system, and 81 procedures applying the Therakos Cellex inline system.

Dissecting the dynamics of SARS-CoV-2 reinfections in blood donors with pauci- or asymptomatic COVID-19 disease course at initial infection.

Background: Understanding the dynamics of SARS-CoV-2 reinfections is crucial for public health policy, vaccine development, and long-term disease management. However, data on reinfections in the general population remains scarce.

Objectives: This study aimed to investigate SARS-CoV-2 antibody dynamics among Austrian blood donors, representing healthy adults, over two years following primary infection and to evaluate the reinfection risk.

Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats.

Background: The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model.

Methods: 6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 10), rhBMP-2 (1.

Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course.

Purpose: Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS.

Collection efficiency of mononuclear cells in offline extracorporeal photopheresis: can processing time be shortened?

Background: Extracorporeal photopheresis (ECP) is a well-established but lengthy and burdensome cell-based therapy for various diseases such as cutaneous T-cell lymphoma, graft-versus-host disease and organ rejection after transplantation. The number of mononuclear cells (MNCs) that needs to be collected to obtain a clinical response to ECP is still under debate. The purpose of this retrospective study was to determine the number of lymphocytes, monocytes and neutrophils in mononuclear cell products (MCP) by flow cytometry and the collection efficiency in the offline ECP setting.

A report on the International Society for Cell & Gene Therapy 2022 Scientific Signature Series, "Therapeutic advances with native and engineered human extracellular vesicles".

The International Society for Cell & Gene Therapy Scientific Signature Series event "Therapeutic Advances With Native and Engineered Human EVs" took place as part of the International Society for Cell & Gene Therapy 2022 Annual Meeting, held from May 4 to 7, 2022, in San Francisco, California, USA. This was the first signature series event on extracellular vesicles (EVs) and a timely reflection of the growing interest in EVs, including both native and engineered human EVs, for therapeutic applications. The event successfully gathered academic and industrial key opinion leaders to discuss the current state of the art in developing and understanding native and engineered EVs and applying our knowledge toward advancing EV therapeutics.

Evaluation of the Potential of Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles to Improve Rotator Cuff Healing: A Pilot Ovine Study.

Background: Despite significant advancements in surgical techniques to repair rotator cuff (RC) injuries, failure rates remain high and novel approaches to adequately overcome the natural biological limits of tendon and enthesis regeneration of the RC are required. Small extracellular vesicles (sEVs) derived from the secretome of human multipotent mesenchymal stromal cells (MSCs) have been demonstrated to modulate inflammation and reduce fibrotic adhesions, and therefore their local application could improve outcomes after RC repair.

Purpose: In this pilot study, we evaluated the efficacy of clinical-grade human umbilical cord (hUC) MSC-derived sEVs (hUC-MSC-sEVs) loaded onto a type 1 collagen scaffold in an ovine model of acute infraspinatus tendon injury to improve RC healing.

GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology.

Extracellular vesicles (EVs) released by a variety of cell types have been shown to act as a natural delivery system for bioactive molecules such as RNAs and proteins. EV therapy holds great promise as a safe and cell-free therapy for many immunological and degenerative diseases. However, translation to clinical application is limited by several factors, including insufficient large-scale manufacturing technologies and low yield.

Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations.

(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules.

Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation.

Human platelet lysate (HPL) is an efficient alternative for animal serum supplements, significantly enhancing stromal cell proliferation. However, the molecular mechanism behind this growth-promoting effect remains elusive. The aim of this study was to investigate the effect of HPL on cell cycle gene expression in different human stromal cells and to identify the main key players that mediate HPL's growth-enhancing effect.

SARS-CoV-2 IgG Levels Allow Predicting the Optimal Time Span of Convalescent Plasma Donor Suitability.

Convalescent plasma (CP) has been in use for the treatment of numerous infectious diseases for more than a century, recently also for coronavirus disease 2019 (COVID-19). A major challenge for this treatment is identifying suitable donors with sufficient levels of functional antibodies and to determine the optimal time span for CP donation. In this retrospective study, we analyzed 189 CP donations of 66 donors regarding anti-SARS-CoV-2 anti-S IgG antibody levels.

When the available blood supply mismatches the needs of the patient.

Background: Substantial regional differences in the genetic patterns related to blood group have been observed across different continents. This diversity means that the blood supply, as an essential part of patient care, is increasingly impacted by global migration. Consequently, the Austrian blood donor population does not match the immigrant patient population.

Large-scale production of extracellular vesicles: Report on the "massivEVs" ISEV workshop.

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, "The Extracellular Vesicle Foundry" (evFOUNDRY) and "Extracellular vesicles from a natural source for tailor-made nanomaterials" (VES4US), organized a workshop entitled "massivEVs" to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during "massivEVs", the most important points raised, and the points of consensus reached after discussion among academia and industry representatives.

Systemic Immune Profile Predicts the Development of Infections in Patients with Spinal Cord Injuries.

Patients with spinal cord injury (SCI) frequently develop infections that may affect quality of life, be life-threatening, and impair their neurological recovery in the acute and subacute injury phases. Therefore, identifying patients with SCI at risk for developing infections in this stage is of utmost importance. We determined the systemic levels of immune cell populations, cytokines, chemokines, and growth factors in 81 patients with traumatic SCI at 4 weeks after injury and compared them with those of 26 age-matched healthy control subjects.

Persistence of Naturally Acquired and Functional SARS-CoV-2 Antibodies in Blood Donors One Year after Infection.

The developmental course of antibodies produced after a SARS-CoV-2 infection has been insufficiently investigated so far. Therefore, the aim of this study was to investigate the dynamics of SARS-CoV-2 antibody levels against the viral nucleocapsid- and spike-protein among Austrian blood donors as a representative group of a supposedly healthy population within the first year after a SARS-CoV-2 infection. The impact of age, sex, vaccination status, AB0-blood group and awareness about the infection was evaluated.

Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury.

Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally.

Heparin and Derivatives for Advanced Cell Therapies.

Heparin and its derivatives are saving thousands of human lives annually, by successfully preventing and treating thromboembolic events. Although the mode of action during anticoagulation is well studied, their influence on cell behavior is not fully understood as is the risk of bleeding and other side effects. New applications in regenerative medicine have evolved supporting production of cell-based therapeutics or as a substrate for creating functionalized matrices in biotechnology.

Correction: Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes.

Correction for 'Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes' by Fabio Perissinotto et al., Nanoscale, 2021, 13, 5224-5233, DOI: .

First-in-human intracochlear application of human stromal cell-derived extracellular vesicles.

Extracellular vesicles (EVs) derived from the secretome of human mesenchymal stromal cells (MSC) contain numerous factors that are known to exert anti-inflammatory effects. MSC-EVs may serve as promising cell-based therapeutics for the inner ear to attenuate inflammation-based side effects from cochlear implantation which represents an unmet clinical need. In an individual treatment performed on a 'named patient basis', we intraoperatively applied allogeneic umbilical cord-derived MSC-EVs (UC-MSC-EVs) produced according to good manufacturing practice.

Seroprevalence of anti-SARS-CoV-2 total antibody is higher in younger Austrian blood donors.

Purpose: Frequently the infection with coronavirus 2 (SARS-CoV-2) can be asymptomatic or provoke only mild symptoms. These cases often remain unnoticed, so it is difficult to estimate the actual numbers of infections. Aim of this study was to determine the seroprevalence of anti-SARS-CoV-2 total antibody in Austrian blood donors.

Human Platelet Lysate for Good Manufacturing Practice-Compliant Cell Production.

Numerous cell-based therapeutics are currently being tested in clinical trials. Human platelet lysate (HPL) is a valuable alternative to fetal bovine serum as a cell culture medium supplement for a variety of different cell types. HPL as a raw material permits animal serum-free cell propagation with highly efficient stimulation of cell proliferation, enabling humanized manufacturing of cell therapeutics within a reasonable timeframe.

Leukocyte-Reactive Antibodies in Female Blood Donors: The Austrian Experience.

Introduction: Antibody-mediated transfusion-related acute lung injury (TRALI) is caused by antibodies against human leukocyte antigens (HLAs) or human neutrophil antigens (HNAs), and is one of the most serious complications associated with transfusion medicine. Prevention strategies like testing allo-exposed female blood donors have not yet been introduced nationwide in Austria. To assess the need and feasibility of routine leukocyte antibody testing, the prevalence of leukocyte-reactive antibodies in an Austrian female donor population was been determined using classical cell-based methods which were compared with a high-throughput bead-based method.

Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes.

Extracellular vesicles (EVs) are a potent intercellular communication system. Such small vesicles transport biomolecules between cells and throughout the body, strongly influencing the fate of recipient cells. Due to their specific biological functions they have been proposed as biomarkers for various diseases and as optimal candidates for therapeutic applications.