The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial.

Purpose: Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP).

Materials And Methods: Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo.

A phase Ib/IIa, randomised, double-blind, multicentre trial to assess the safety and efficacy of expanded Cx611 allogeneic adipose-derived stem cells (eASCs) for the treatment of patients with community-acquired bacterial pneumonia admitted to the intensive care unit.

Background: Community-acquired bacterial pneumonia (CABP) can lead to sepsis and is associated with high mortality rates in patients presenting with shock and/or respiratory failure and who require mechanical ventilation and admission to intensive care units, thus reflecting the limited effectiveness of current therapy. Preclinical studies support the efficacy of expanded allogeneic adipose-derived mesenchymal stem cells (eASCs) in the treatment of sepsis. In this study, we aim to test the safety, tolerability and efficacy of eASCs as adjunctive therapy in patients with severe CABP (sCABP).

Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2.

Background: Mesenchymal stem cells (MSCs) activate the endogenous immune regulatory system, inducing a therapeutic effect in recipients. MSCs have demonstrated the ability to modulate the differentiation of myeloid cells toward a phagocytic and anti-inflammatory profile. Allogeneic, adipose-derived MSCs (ASCs) have been investigated for the management of complex perianal fistula, with darvadstrocel being the first ASC therapy approved in Europe in March 2018.

Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice.

Background: Adult mesenchymal stem cells (MSCs) improve the host response during experimental sepsis in animals. MSCs from various sources express a procoagulant activity that has been linked to the expression of tissue factor. This study sought to determine the role of tissue factor associated with adipose-derived MSCs (ASCs) in their procoagulant and antibacterial effects during pneumonia-derived sepsis.

Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae.

Adult mesenchymal stem cells exert immunomodulatory effects that might improve the host response during sepsis. Knowledge on the effect of adipose-derived mesenchymal stem cells (ASCs) in sepsis is limited. Klebsiella (K.

Extracellular Vesicles Released by Allogeneic Human Cardiac Stem/Progenitor Cells as Part of Their Therapeutic Benefit.

The positive effects of therapeutic human allogeneic cardiac stem/progenitor cells (hCPC) in terms of cardiac repair/regeneration are very likely mediated by paracrine effects. Our previous studies revealed the advantageous immune interactions of allogeneic hCPC and proposed them as part of the positive paracrine effects occurring upon their application postmyocardial infarction (MI). Currently, extracellular vesicles/exosomes (EV/Exs) released by stem/progenitor cells are also proposed as major mediators of paracrine effects of therapeutic cells.

Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis.

Background: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats.

Methods: Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS).

Identification of Potential Plasma microRNA Stratification Biomarkers for Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells in Rheumatoid Arthritis.

The ability to identify and stratify patients that will respond to specific therapies has been transformational in a number of disease areas, particularly oncology. It is anticipated that this will also be the case for cell-based therapies, particularly in complex and heterogeneous diseases such as rheumatoid arthritis (RA). Recently, clinical results with expanded allogenic adipose-derived mesenchymal stem cells (eASCs) have indicated clinical efficacy in highly refractory RA patients.

Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells.

In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell-cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles.

Adipose mesenchymal stromal cell function is not affected by methotrexate and azathioprine.

Given their capacity to modulate the immune response, adipose mesenchymal stem or stromal cells (ASCs) have been used as therapeutic tools to treat chronic inflammatory and autoimmune diseases both in preclinical and clinical studies. Patients enrolled in such clinical trials are often concomitantly treated with immunomodulatory drugs such as methotrexate (MTX) or azathioprine (AZA). Therefore it is necessary to investigate the possible impact of these drugs on ASC function to learn if there are any interactions that would affect the therapeutic effects of either component and thus the clinical outcome of the trials.

Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity.

The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells.

Nonleukemic myeloid dendritic cells obtained from autologous stem cell products elicit antileukemia responses in patients with acute myeloid leukemia.

Background: Dendritic cell (DC)-based immunotherapeutic protocols are being developed to treat acute myeloid leukemia (AML). So far, DCs for clinical use are obtained from leukemic blasts or from monocytes, after 6 to 10 days of ex vivo culture. However, DC precursors are easily driven to DCs in short-term culture.

Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients.

The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients.

Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients.

The melanocyte differentiation Ag RAB38/NY-MEL-1 was identified by serological expression cloning (SEREX) and is expressed in the vast majority of melanoma lesions. The immunogenicity of RAB38/NY-MEL-1 has been corroborated previously by the frequent occurrence of specific Ab responses in melanoma patients. To elucidate potential CD8 T cell responses, we applied in vitro sensitization with overlapping peptides spanning the RAB38/NY-MEL-1 protein sequence and the reverse immunology approach.

Extracellular xylanases from two pathogenic races of Fusarium oxysporum f. sp. ciceris: enzyme production in culture and purification and characterization of a major isoform as an alkaline endo-beta-(1,4)-xylanase of low molecular weight.

Fusarium oxysporum f. sp. ciceris, the causal agent of Fusarium wilt of chickpea, comprises eight pathogenic races and two pathotypes.