Benefits and limits of decellularization on mass-spectrometry-based extracellular matrix proteome analysis of mouse kidney.

The extracellular matrix (ECM) is composed of collagens, ECM glycoproteins, and proteoglycans (also named core matrisome proteins) that are critical for tissue structure and function, and matrisome-associated proteins that balance the production and degradation of the ECM proteins. The identification and quantification of core matrisome proteins using mass spectrometry is often hindered by their low abundance and their propensity to form macromolecular insoluble structures. In this study, we aimed to investigate the added value of decellularization in identifying and quantifying core matrisome proteins in mouse kidney.

Recent Advances in Mesenchymal Stem/Stromal Cell-Based Therapy for Alcohol-Associated Liver Disease and Non-alcoholic Fatty Liver Disease.

Alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) represent pathological conditions that include many distinct stages, potentially leading to the final stage of cirrhotic liver. To date, liver transplantation is the sole successful treatment with concomitant limitations related to donor organ shortage and the need of life-long immunosuppressive therapy. Recently, cell-based therapies for ALD and NAFLD have been proposed with mesenchymal stem/stromal cells (MSCs) as promising effectors.

MFGE-8 identified in fetal mesenchymal-stromal-cell-derived exosomes ameliorates acute hepatic failure pathology.

Liver transplantation is the gold-standard therapy for acute hepatic failure (AHF) with limitations related to organ shortage and life-long immunosuppressive therapy. Cell therapy emerges as a promising alternative to transplantation. We have previously shown that IL-10 and Annexin-A1 released by amniotic fluid human mesenchymal stromal cells (AF-MSCs) and their hepatocyte progenitor-like (HPL) or hepatocyte-like (HPL) cells induce liver repair and downregulate systemic inflammation in a CCl-AHF mouse model.

Reviewing the Regulators of COL1A1.

The collagen family contains 28 proteins, predominantly expressed in the extracellular matrix (ECM) and characterized by a triple-helix structure. Collagens undergo several maturation steps, including post-translational modifications (PTMs) and cross-linking. These proteins are associated with multiple diseases, the most pronounced of which are fibrosis and bone diseases.

Amniotic Fluid-Derived Mesenchymal Stem/Stromal Cell-Derived Secretome and Exosomes Improve Inflammation in Human Intestinal Subepithelial Myofibroblasts.

Inflammatory Bowel Diseases (IBDs) are characterized by chronic relapsing inflammation of the gastrointestinal tract. The mesenchymal stem/stromal cell-derived secretome and secreted extracellular vesicles may offer novel therapeutic opportunities in patients with IBD. Thus, exosomes may be utilized as a novel cell-free approach for IBD therapy.

General consensus on multimodal functions and validation analysis of perinatal derivatives for regenerative medicine applications.

Perinatal tissues, such as placenta and umbilical cord contain a variety of somatic stem cell types, spanning from the largely used hematopoietic stem and progenitor cells to the most recently described broadly multipotent epithelial and stromal cells. As perinatal derivatives (PnD), several of these cell types and related products provide an interesting regenerative potential for a variety of diseases. Within COST SPRINT Action, we continue our review series, revising and summarizing the modalities of action and proposed medical approaches using PnD products: cells, secretome, extracellular vesicles, and decellularized tissues.

Liver Regeneration by Hematopoietic Stem Cells: Have We Reached the End of the Road?

The liver is the organ with the highest regenerative capacity in the human body. However, various insults, including viral infections, alcohol or drug abuse, and metabolic overload, may cause chronic inflammation and fibrosis, leading to irreversible liver dysfunction. Despite advances in surgery and pharmacological treatments, liver diseases remain a leading cause of death worldwide.

Gene Expression Monotonicity across Bladder Cancer Stages Informs on the Molecular Pathogenesis and Identifies a Prognostic Eight-Gene Signature.

Despite advancements in molecular classification, tumor stage and grade still remain the most relevant prognosticators used by clinicians to decide on patient management. Here, we leverage publicly available data to characterize bladder cancer (BLCA)'s stage biology based on increased sample sizes, identify potential therapeutic targets, and extract putative biomarkers. A total of 1135 primary BLCA transcriptomes from 12 microarray studies were compiled in a meta-cohort and analyzed for monotonal alterations in pathway activities, gene expression, and co-expression patterns with increasing stage (Ta-T1-T2-T3-T4), starting from the non-malignant tumor-adjacent urothelium.

The Potential Clinical Use of Stem/Progenitor Cells and Organoids in Liver Diseases.

The liver represents the most important metabolic organ of the human body. It is evident that an imbalance of liver function can lead to several pathological conditions, known as liver failure. Orthotropic liver transplantation (OLT) is currently the most effective and established treatment for end-stage liver diseases and acute liver failure (ALF).

Success Stories and Challenges Ahead in Hematopoietic Stem Cell Gene Therapy: Hemoglobinopathies as Disease Models.

Gene therapy is a relatively novel field that amounts to around four decades of continuous growth with its good and bad moments. Currently, the field has entered the clinical arena with the ambition to fulfil its promises for a permanent fix of incurable genetic disorders. Hemoglobinopathies as target diseases and hematopoietic stem cells (HSCs) as target cells of genetic interventions had a major share in the research effort toward efficiently implementing gene therapy.

Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases.

Liver dysfunctions are classified into acute and chronic diseases, which comprise a heterogeneous group of pathological features and a high mortality rate. Liver transplantation remains the gold-standard therapy for most liver diseases, with concomitant limitations related to donor organ shortage and lifelong immunosuppressive therapy. A concept in liver therapy intends to overcome these limitations based on the secreted extracellular vesicles (EVs; microvesicles and exosomes) by mesenchymal stem/stromal cells (MSCs).

P-Related Protein Accelerates Human Mesenchymal Stromal Cell Migration by Modulating VLA-5 Interactions with Fibronectin.

P-related protein (PZR), a Noonan and Leopard syndrome target, is a member of the transmembrane Immunoglobulin superfamily. Its cytoplasmic tail contains two immune-receptor tyrosine-based inhibitory motifs (ITIMs), implicated in adhesion-dependent signaling and regulating cell adhesion and motility. PZR promotes cell migration on the extracellular matrix (ECM) molecule, fibronectin, by interacting with SHP-2 (Src homology-2 domain-containing protein tyrosine phosphatase-2), a molecule essential for skeletal development and often mutated in Noonan and Leopard syndrome patients sharing overlapping musculoskeletal abnormalities and cardiac defects.

Proteomics Analysis of Formalin Fixed Paraffin Embedded Tissues in the Investigation of Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of death in men worldwide. The molecular features, associated with the onset and progression of the disease, are under vigorous investigation. Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources for large-scale studies; however, their application in proteomics is limited due to protein cross-linking.

Functional secretome analysis reveals Annexin-A1 as important paracrine factor derived from fetal mesenchymal stem cells in hepatic regeneration.

Background: Human mesenchymal stem/stromal cells (MSCs) and their secreted molecules exert beneficial effects in injured tissues by promoting tissue regeneration and angiogenesis and by inhibiting inflammation and fibrosis. We have previously demonstrated that the therapeutic activity of fetal MSCs derived from amniotic fluid (AF-MSCs) and their hepatic progenitor-like cells (HPL) is mediated by paracrine effects in a mouse model of acute hepatic failure (AHF).

Methods: Herein, we have combined proteomic profiling of the AF-MSCs and HPL cell secretome with ex vivo and in vivo functional studies to identify specific soluble factors, which underpin tissue regeneration in AHF.

Proteomics based identification of KDM5 histone demethylases associated with cardiovascular disease.

Background: The increased prevalence of cardiovascular disease (CVD) indicates a demand for novel therapeutic approaches. Proteome analysis of vascular tissues from animal models and humans with CVD could lead to the identification of novel druggable targets.

Methods: LC-MS/MS analysis of thoracic aortas from three mouse models of non-diabetic and diabetic (streptozotocin (STZ)-induced) atherosclerosis followed by bioinformatics/pathway analysis was performed.

Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention.

Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted.

Application of adipose-derived stromal cells in fat grafting: Basic science and literature review.

Autologous fat is considered the ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of 'cell-assisted lipotransfer'.

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Past, Present, and Future.

The concept of Regenerative Medicine combined with Cell based Therapy and Tissue Engineering represents the fourth pillar of healthcare and provides a promising approach for the treatment of serious diseases. Recently, cell based therapies are focused on the use of mesenchymal stem/stromal cells (MSCs). Human MSCs, that represent a mesoderm derived population of progenitors, are easily expanded in culture.

miR-193a-3p interaction with HMGB1 downregulates human endothelial cell proliferation and migration.

Circulating endothelial colony forming cells (ECFCs) contribute to vascular repair where they are a target for therapy. Since ECFC proliferative potential is increased in cord versus peripheral blood and to define regulatory factors controlling this proliferation, we compared the miRNA profiles of cord blood and peripheral blood ECFC-derived cells. Of the top 25 differentially regulated miRNAs selected, 22 were more highly expressed in peripheral blood ECFC-derived cells.

miR-26a Mediates Adipogenesis of Amniotic Fluid Mesenchymal Stem/Stromal Cells via PTEN, Cyclin E1, and CDK6.

Recent findings indicate that microRNAs (miRNAs) are critical for the regulatory network of adipogenesis in human mesenchymal stem/stromal cells (MSCs). Fetal MSCs derived from amniotic fluid (AF-MSCs) represent a population of multipotent stem cells characterized by a wide range of differentiation properties that can be applied in cell-based therapies. In this study, miRNA microarray analysis was performed to assess miRNA expression in terminal differentiated AF-MSCs into adipocyte-like cells (AL cells).

Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models.

Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet.

Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study.

Purpose: Urothelial bladder cancer presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of noninvasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent urothelial bladder cancer was conducted.

Low mutational burden of eight genes involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways in female genital tract primary melanomas.

Mucosal melanomas exhibit discrete genetic features compared to cutaneous melanoma. Limited studies on gynecological melanomas revealed significant heterogeneity and low mutational burden. To gain further insight into their genetics and DNA repair efficiency, we systematically investigated the status of eight genes whose products are critically involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways, including BRAF, NRAS, HRAS, KRAS, c-KIT, PI3K, GNAQ, and GNA11, in a series of 16 primary gynecological melanomas, covering all anatomical locations, ranging from stages I to III.

The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks.

Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic" chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4 antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition.