Co-infusion of mesenchymal stromal cells to prevent GVHD after allogeneic hematopoietic cell transplantation from HLA-mismatched unrelated donors after reduced-intensity conditioning: a double-blind randomized study and literature review.

Background: Mesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD).

Methods: Based on our previous pilot study, we established a multicenter, prospective, randomized, double-blind trial evaluating the efficacy of co-infusing third-party MSC (1.5-3 × 10/kg) versus placebo on the day of HSC transplantation (HCT) to prevent GVHD in recipients of HLA-mismatched unrelated donors after reduced-intensity conditioning.

A management model in blood, tissue and cell establishments to ensure rapid and sustainable patient access to advanced therapy medicinal products in Europe.

Blood, tissue and cell establishments (BTCs) stand out in the management of donor selection, procurement and processing of all types of substances of human origin (SoHO). In the last decades, the framework created around BTCs, including hospitals and national health system networks, and their links to research, development and innovation organizations and agencies have spurred their involvement in the study of groundbreaking advanced therapy medicinal products (ATMP). To further improve strategic synergies in the development of ATMPs, it will be required to promote intra- and inter-European collaborations by creating an international network involving BTCs and major stakeholders (i.

Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis.

Introduction: Poor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT.

Methods: We prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT.

Clinical and MRI Evolution After Local Injection of Bone Marrow-Derived Mesenchymal Stem Cells in Perianal Fistulae in Crohn's Disease: Results From a Prospective Monocentric Study.

Background: Local injection of adipose tissue-derived mesenchymal stem cells [MSCs] is effective in fistulizing perianal Crohn's disease [CD]. Less is known about bone marrow-derived MSCs and little is known about predictive factors of response and magnetic resonance imaging [MRI] evolution of the fistulae after MSC injection. Our aims were to evaluate the safety and clinical outcome of bone marrow-derived MSC injection for perianal fistulizing CD, to evaluate the MRI evolution of the fistulae and to identify factors associated with fistula closure.

Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial.

Background: Treatment of acute respiratory distress syndrome (ARDS) associated with COronaVIrus Disease-2019 (COVID-19) currently relies on dexamethasone and supportive mechanical ventilation, and remains associated with high mortality. Given their ability to limit inflammation, induce immune cells into a regulatory phenotype and stimulate tissue repair, mesenchymal stromal cells (MSCs) represent a promising therapy for severe and critical COVID-19 disease, which is associated with an uncontrolled immune-mediated inflammatory response.

Methods: In this phase I-II trial, we aimed to evaluate the safety and efficacy of 3 intravenous infusions of bone marrow (BM)-derived MSCs at 3-day intervals in patients with severe COVID-19.

[Cellular immunotherapy at the University Hospital of Liege : advances, challenges and prospects].

Cellular immunotherapy consists in using the cells of the immune system as a therapeutic weapon. In this constantly evolving field, the therapeutic strategies developed at the University Hospital of Liege are hematopoietic stem cell transplantation, mesenchymal stromal cells and targeted therapy with CAR-T cells (Chimeric Antigen Receptor T cells). The first two modalities represent a form of non-targeted cell therapy that has been developed over the past decades.

Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes.

Unlabelled: Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC).

Infusion of Allogeneic Mesenchymal Stromal Cells After Liver Transplantation: A 5-Year Follow-Up.

Various properties of mesenchymal stromal cells (MSCs) might be particularly of interest after liver transplantation (LT). In this article, we report the long-term results of a prospective, controlled, and first-in-human phase 1 study evaluating the safety of a single MSC infusion after LT. A total of 10 LT recipients treated with standard immunosuppression received 1.

Mesenchymal Stem Cell Injection in Crohn's Disease Strictures: A Phase I-II Clinical Study.

Background And Aim: Mesenchymal stem cells [MSCs] have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn's disease [CD] strictures. In this phase I-II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures.

Methods: CD patients with a short [less than 5 cm in length] non-passable stricture accessible by ileocolonoscopy were included.

MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process.

Following European regulation 1394/2007, mesenchymal stromal cell (MSCs) have become an advanced therapy medicinal product (ATMP) that must be produced following the good manufacturing practice (GMP) standards. We describe the upgrade of our existing clinical-grade MSC manufacturing process to obtain GMP certification. Staff organization, premises/equipment qualification and monitoring, raw materials management, starting materials, technical manufacturing processes, quality controls, and the release, thawing and infusion were substantially reorganized.

Mesenchymal Stromal Cells in Solid Organ Transplantation.

Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These expectations arise from a significant number of both transplant- and non-transplant-related experimental studies investigating the complex anti-inflammatory, immunomodulatory, and tissue-repair properties of MSCs. Promising preclinical results have prompted clinical trials using MSC-based therapy in SOT.

Comparison of Mesenchymal Stromal Cells From Different Origins for the Treatment of Graft-vs.-Host-Disease in a Humanized Mouse Model.

Mesenchymal stromal cells (MSCs) have potent immunomodulatory properties that make them an attractive tool against graft- vs.-host disease (GVHD). However, despite promising results in phase I/II studies, bone marrow (BM-) derived MSCs failed to demonstrate their superiority over placebo in the sole phase III trial reported thus far.

Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study.

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs (∼2 × 10/kg) on day 3 ± 2 post-transplant and were compared to 10 concurrent controls.

Infusion of bone marrow derived multipotent mesenchymal stromal cells for the treatment of steroid-refractory acute graft-versus-host disease: a multicenter prospective study.

The prognosis of steroid-refractory acute graft-versus-host disease (aGVHD) remains poor and better treatments are urgently needed. Multipotent mesenchymal stromal cell (MSC)-based therapy emerged as a promising approach but response rates were highly variable across studies. We conducted a multicenter prospective study assessing the efficacy of 1-2 infusion(s) of cryopreserved, third-party donor bone marrow-derived MSCs for treating grade II-IV steroid-refractory or -dependent aGVHD in a series of 33 patients.

Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.

Background & Aims: Mesenchymal stromal cell (MSC) infusion could be a means to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase I study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients.

Methods: Ten liver transplant recipients under standard immunosuppression received 1.

Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases.

Background: Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair.

Aim: To review the current data on mesenchymal stromal cell therapy in IBD.

Clinical-scale expansion of mesenchymal stromal cells: a large banking experience.

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn's disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007.

Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT).

Rationale for the potential use of mesenchymal stromal cells in liver transplantation.

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing cells that reside essentially in the bone marrow as a non-hematopoietic cell population, but may also be isolated from the connective tissues of most organs. MSCs represent a heterogeneous population of adult, fibroblast-like cells characterized by their ability to differentiate into tissues of mesodermal lineages including adipocytes, chondrocytes and osteocytes. For several years now, MSCs have been evaluated for their in vivo and in vitro immunomodulatory and 'tissue reconstruction' properties, which could make them interesting in various clinical settings, and particularly in organ transplantation.

RETRACTED: Human bone marrow, umbilical cord or liver mesenchymal stromal cells fail to improve liver function in a model of CCl4-induced liver damage in NOD/SCID/IL-2Rγ(null) mice.

This article has been removed: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

Impact of cotransplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning.

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft-versus-host disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans.

Mesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion.

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue.