Human metapneumovirus (hMPV) is a significant cause of respiratory infections worldwide, particularly in young children, the elderly, and immunocompromised individuals. Since its discovery in 2001, hMPV has been recognized as a major contributor to acute respiratory tract infections, along with respiratory syncytial virus (RSV) and influenza. This review explores the virology, epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and recent advances in therapeutic and preventive strategies for hMPV infection. By consolidating current knowledge, we aim to highlight the importance of hMPV in public health and the need for continued research to address its clinical and economic burdens.

Cancer is a leading cause of death worldwide and a major burden on the healthcare system. Current treatment methods are limited as they have low selectivity, unspecific targeting and increasing multidrug resistance. Therefore, newer modes of therapeutic strategies need to be developed. Anticancer peptides (ACP) are small bioactive peptides that have the ability to be selective and toxic to cancer, with a high efficiency in cell penetration and internalization and low risk of inducing multidrug resistance. ACPs have multitude of mechanisms giving them the ability to target multiple cancer types as well as both slow growing and metabolically active cancers. Recently, a large number of literature papers examine the structure, mechanisms of action, synthesis, modifications and other non-direct cancer treatment applications of ACPs. A growing aspect in all areas of research and development especially in peptide drug discovery is now Artificial Intelligence (AI). It enables large amounts of data to be processed quickly and allows for rapid predictions hence the increased discovery of new ACPs. In this review, we discuss the structure, mechanisms of action, synthesis of ACPs and the different types of AI models, their algorithms and the ACPs prediction models currently available.

Metabolites produced by dysbiotic intestinal microbiota can influence disease pathophysiology by participating in ligand–receptor interactions. Our aim was to investigate the differential expression of metabolite receptor (MR) genes between inflammatory bowel disease (IBD), healthy individuals (HIs), and disease controls in order to identify possible interactions with inflammatory and fibrotic pathways in the intestine. RNA-sequencing datasets containing 643 Crohn’s disease (CD) patients, 467 ulcerative colitis (UC) patients and 295 HIs, and 4 Campylobacter jejuni-infected individuals were retrieved from the Sequence Read Archive, and differential expression was performed using the RaNA-seq online platform. The identified differentially expressed MR genes were used for correlation analysis with up- and downregulated genes in IBD, as well as functional enrichment analysis using a R based pipeline. Overall, 15 MR genes exhibited dysregulated expression in IBD. In inflamed CD, the hydroxycarboxylic acid receptors 2 and 3 (HCAR2, HCAR3) were upregulated and were associated with the recruitment of innate immune cells, while, in the non-inflamed CD ileum, the cannabinoid receptor 1 (CNR1) and the sphingosine-1-phospate receptor 4 (S1PR4) were downregulated and were involved in the regulation of B-cell activation. In inflamed UC, the upregulated receptors HCAR2 and HCAR3 were more closely associated with the process of TH-17 cell differentiation, while the pregnane X receptor (NR1I2) and the transient receptor potential vanilloid 1 (TRPV1) were downregulated and were involved in epithelial barrier maintenance. Our results elucidate the landscape of metabolite receptor expression in IBD, highlighting associations with disease-related functions that could guide the development of new targeted therapies.

Background Oncostatin-M (OSM) is associated with antitumor necrosis factor (anti-TNF)-alpha resistance in inflammatory bowel disease (IBD) and fibrosis in inflammatory diseases. We studied the expression of OSM and its receptors (OSMR, gp130) on intestinal subepithelial myofibroblasts (SEMFs) and the effect of OSM stimulation on SEMFs. Methods The mRNA and protein expression of OSM, OSMR, gp130, and several fibrotic and chemotactic factors were studied in mucosal biopsies and isolated human intestinal SEMFs of patients with IBD and healthy controls (HCs) and in a model of human intestinal organoids (HIOs). Subepithelial myofibroblasts and HIOs were stimulated with OSM and interleukin (IL)-1 alpha/TNF-alpha. RNAseq data of mucosal biopsies were also analyzed. Results Oncostatin-M receptors and gp130 were overexpressed in mucosal biopsies of patients with IBD (P < .05), especially in inflamed segments (P < .05). The expression of OSM, OSMR, and gp130 in SEMFs from HCs was increased after stimulation with IL-1 alpha/TNF-alpha (P < .001; P < .01; P < .01). The expression of CCL2, CXCL9, CXCL10, and CXCL11 was increased in SEMFs from patients with IBD and HCs after stimulation with OSM in a dose-dependent manner (P < .001; P < .05; P < .001; P < .001) and was further increased after prestimulation with IL-1 alpha/TNF-alpha (P < .01 vs OSM-alone). Similar results were yielded after stimulation of HIOs (P < .01). Oncostatin-M did not induce the expression of collagen I, III, and fibronectin. Oncostatin-M receptor expression was positively correlated with CCL2, CXCL9, CXCL10, and CXCL11 expression in mucosal biopsies (P < .001; P < .001; P = .045; P = .033). Conclusions Human SEMFs overexpress OSMR in an inflammatory microenvironment. Oncostatin-M may promote inflammation in IBD via its stimulatory effects on SEMFs, which primarily involve chemoattraction of immune cells to the intestinal mucosa.

Background and aims: Monocyte recruitment in the lamina propria and inflammatory phenotype driven by the mucosal microenvironment is critical for the pathogenesis of inflammatory bowel disease. However, the stimuli responsible remain largely unknown. Recent works have focused on stromal cells, the main steady-state cellular component in tissue, as they produce pro-inflammatory chemokines that contribute to the treatment-resistant nature of IBD. Methods: We studied the regulation of these processes by examining the communication patterns between stromal and myeloid cells in ileal Crohn’s disease (CD) using a complete single-cell whole tissue sequencing analysis pipeline and in vitro experimentation in mesenchymal cells. Results: We report expansion of S4 stromal cells and monocyte-like inflammatory macrophages in the inflamed mucosa and describe interactions that may establish sustained local inflammation. These include expression of CCL2 by S1 fibroblasts to recruit and retain monocytes and macrophages in the mucosa, where they receive signals for proliferation, survival, and differentiation to inflammatory macrophages from S4 stromal cells through molecules such as MIF, IFNγ, and FN1. The overexpression of CCL2 in ileal CD and its stromal origin was further demonstrated in vitro by cultured mesenchymal cells and intestinal organoids in the context of an inflammatory milieu. Conclusions: Our findings outline an extensive cross-talk between stromal and myeloid cells, which may contribute to the onset and progression of inflammation in ileal Crohn’s disease. Understanding the mechanisms underlying monocyte recruitment and polarization, as well as the role of stromal cells in sustaining inflammation, can provide new avenues for developing targeted therapies to treat IBD.

Background/Objectives: The role of the gut microbiome in cancer biology has become an increasingly prominent area of research, particularly regarding the role of microbial metabolites and their receptors (MMRs). These metabolites, through the various gut-organ axes, have been proven to influence several pathogenetic mechanisms. This study conducted a comprehensive pan-cancer analysis of MMR transcriptomic profiles across twenty-three cancer types, exploring the mechanisms through which they can influence cancer development and progression. Methods: Utilizing both cancer cell lines from CCLE (Cancer Cell Line Encyclopedia) and human tumor samples from TCGA (The Cancer Gene Atlas), we analyzed 107 MMRs interacting with microbial metabolites such as short-chain fatty acids, bile acids, indole derivatives, and others while studying their interactions with key known cancer genes. Results: Our results revealed that certain MMRs, such as GPR84 and serotonin receptors, are consistently upregulated in various malignancies, while others, like ADRA1A, are frequently downregulated, suggesting diverse roles in cancer pathophysiology. Furthermore, we identified significant correlations between MMR expression and cancer hallmark genes and pathways, including immune evasion, proliferation, and metastasis. Conclusions: These findings suggest that the interactions between microbial metabolites and MMRs may serve as potential biomarkers for cancer diagnosis, prognosis, and therapy, highlighting their therapeutic potential. This study underscores the significance of the microbiota-cancer axis and provides novel insights into microbiome-based strategies for cancer treatment.

Pluripotent stem cells are key players in regenerative medicine. Embryonic pluripotent stem cells, despite their significant advantages, are associated with limitations such as their inadequate availability and the ethical dilemmas in their isolation and clinical use. The discovery of very small embryonic-like (VSEL) stem cells addressed the aforementioned limitations, but their isolation technique remains a challenge due to their small cell size and their efficiency in isolation. Here, we report a simplified and effective approach for the isolation of small pluripotent stem cells derived from human peripheral blood. Our approach results in a high yield of small blood stem cell (SBSC) population, which expresses pluripotent embryonic markers (e.g., Nanog, SSEA-3) and the Yamanaka factors. Further, a fraction of SBSCs also co-express hematopoietic markers (e.g., CD45 and CD90) and/or mesenchymal markers (e.g., CD29, CD105 and PTH1R), suggesting a mixed stem cell population. Finally, quantitative proteomic profiling reveals that SBSCs contain various stem cell markers (CD9, ITGA6, MAPK1, MTHFD1, STAT3, HSPB1, HSPA4), and Transcription reg complex factors (e.g., STAT5B, PDLIM1, ANXA2, ATF6, CAMK1). In conclusion, we present a novel, simplified and effective isolating process that yields an abundant population of small-sized cells with characteristics of pluripotency from human peripheral blood.

Idiopathic pulmonary fibrosis (IPF) is caused by progressive lung tissue impairment due to extended chronic fibrosis, and it has no known effective treatment. The use of conditioned media (CM) from an immortalized human adipose mesenchymal stem cell line could be a promising therapeutic strategy, as it can reduce both fibrotic and inflammatory responses. We aimed to investigate the anti-inflammatory and anti-fibrotic effect of CM on human pulmonary subepithelial myofibroblasts (hPSM) and on A549 pulmonary epithelial cells, treated with pro-inflammatory or pro-fibrotic mediators. CM inhibited the proinflammatory cytokine-induced mRNA and protein production of various chemokines in both hPSMs and A549 cells. It also downregulated the mRNA expression of IL-1α, but upregulated IL-1β and IL-6 mRNA production in both cell types. CM downregulated the pro-fibrotic-induced mRNA expression of collagen Type III and the migration rate of hPSMs, but upregulated fibronectin mRNA production and the total protein collagen secretion. CM’s direct effect on the chemotaxis and cell recruitment of immune-associated cells, and its indirect effect on fibrosis through the significant decrease in the migration capacity of hPSMs, makes it a plausible candidate for further development towards a therapeutic treatment for IPF.

Abstract Background We have previously shown that human subepithelial myofibroblasts (SEMFs), which are of mesenchymal origin, express the receptor of Oncostatin M (OSM), which is further induced when SEMFs are previously exposed to IL-1α and TNF-α. Human Intestinal Organoids (HIOs), derived from embryonic stem cells (ESC), form epithelial crypts consisting of several subtypes of epithelial cells and are surrounded by cells of mesenchymal origin. Recently, we reported that the mesenchymal component of HIOs is gradually reduced, as culture passages increase. The aim of our study was to examine the effect of exogenous OSM on fibrotic and pro-inflammatory marker expression of HIOs, with and without the combined presence of IL-1α and TNF-α. Methods The human ESC line (H1)-derived HIOs were developed using a commercially available kit and characterized by immunofluorescence in all differentiation stages. HIOs from passage 2 were stimulated with either 100ng/ml OSM for 12 hours or 5ng/ml IL-1α and 50ng/ml TNF-α for 24 hours and then with 100ng/ml OSM for 12 hours. mRNA expression of fibrotic markers, Collagen Type I, III, and Fibronectin, and pro-inflammatory markers, CCL2, CXCL10 and CXCL11 were examined by reverse transcription quantitative PCR. Results OSM alone significantly downregulated both Collagen Type I and III mRNA expression, and had no effect on Fibronectin expression. When HIOs were previously exposed to IL-1α and TNF-α, however, OSM stimulation resulted in significant upregulation of Collagen Type I and Fibronectin, and had no effect on Collagen Type III. Regarding the pro-inflammatory marker expression, OSM alone induced the expression of CCL2, CXCL10 and CXCL11, with a greater effect observed when HIOs were previously exposed to IL-1α and TNF-α. Conclusion Our findings indicate that OSM induces the expression of both fibrotic and pro-inflammatory factors in early passages of HIOs, previously exposed to IL-1a and TNF-a, as has been previously observed on SEMFs. Since the mesenchymal cell component of HIOs is strongly present in early passages and OSM’s receptor is mainly found to be expressed in these cells, our results suggest OSM affects HIOs via the cells that are of mesenchymal origin.

Mesenchyme Stem Cells (MSCs) are the most used types of stem cells in regenerative medicine. Regenerative medicine is a rapidly emerging medicine section that creates new methods to regrow, restore, and replace diseased and damaged tissues, organs, and cells. Scholars have shown a positive correlation between MSCs-based therapies and successful treatment of diseases like cardiac ischemia, cartilage problems, bone diseases, diabetes, and even neurological disorders. Although MSCs have several varying features that make them unique, their immuno-regulatory effects in tissue repair emerge from their secretion of paracrine growth factors, exosomes, and cytokines. These cells secrete a secretome, which has regenerative and reparative properties that lead to injury amelioration, immune modulation, or fibrosis reduction. Recent studies have shown that the administration MCSs derived conditioned medium (MSCs-CM) in acute doses in humans is safe and well-tolerated. Studies from animal models and human clinical trials have also shown that they are efficacious tools in regenerative medicine. In this review, we will explore the therapeutic potential of MSCs-CM in pulmonary fibrosis, with further insight into the treatment of Idiopathic Pulmonary Fibrosis (IPF).

IntroductionExtracellular matrix turnover, a ubiquitous dynamic biological process, can be diverted to fibrosis. The latter can affect the intestine as a serious complication of Inflammatory Bowel Diseases (IBD) and is resistant to current pharmacological interventions. It embosses the need for out-of-the-box approaches to identify and target molecular mechanisms of fibrosis.Methods and resultsIn this study, a novel mRNA sequencing dataset of 22 pairs of intestinal biopsies from the terminal ileum (TI) and the sigmoid of 7 patients with Crohn’s disease, 6 with ulcerative colitis and 9 control individuals (CI) served as a validation cohort of a core fibrotic transcriptomic signature (FIBSig), This signature, which was identified in publicly available data (839 samples from patients and healthy individuals) of 5 fibrotic disorders affecting different organs (GI tract, lung, skin, liver, kidney), encompasses 241 genes and the functional pathways which derive from their interactome. These genes were used in further bioinformatics co-expression analyses to elucidate the site-specific molecular background of intestinal fibrosis highlighting their involvement, particularly in the terminal ileum. We also confirmed different transcriptomic profiles of the sigmoid and terminal ileum in our validation cohort. Combining the results of these analyses we highlight 21 core hub genes within a larger single co-expression module, highly enriched in the terminal ileum of CD patients. Further pathway analysis revealed known and novel inflammation-regulated, fibrogenic pathways operating in the TI, such as IL-13 signaling and pyroptosis, respectively.DiscussionThese findings provide a rationale for the increased incidence of fibrosis at the terminal ileum of CD patients and highlight operating pathways in intestinal fibrosis for future evaluation with mechanistic and translational studies.

Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being the predominant denominator for long-term complications. Epithelial and mesenchymal 2D cultures are highly utilized in vitro models for the preclinical evaluation of anti-inflammatory and antifibrotic therapies. More recently, human intestinal organoids (HIOs), a new 3D in vitro model derived from pluripotent stem cells, have the advantage to closely resemble the architecture of the intestinal mucosa. However, the appropriate timing for the study of inflammatory and fibrotic responses, during HIO development, has not been adequately investigated. We developed HIOs from the human embryonic stem cell line, H1, and examined the expression of mesenchymal markers during their maturation process. We also investigated the effect of inflammatory stimuli on the expression of fibrotic and immunological mediators. Serial evaluation of the expression of mesenchymal and extracellular matrix (ECM) markers revealed that HIOs have an adequately developed mesenchymal component, which gradually declines through culture passages. Specifically, CD90, collagen type I, collagen type III, and fibronectin were highly expressed in early passages but gradually diminished in late passages. The proinflammatory cytokines IL-1α and TNF-α induced the mRNA expression of fibronectin, collagen types I and III, tissue factor (TF), and alpha-smooth muscle actin (α-SMA) primarily in early passages. Similarly, HIOs elicited strong mRNA and protein mesenchymal (CXCL10) and epithelial (CXCL1, CCL2, CXCL8, and CCL20) chemokine responses in early but not late passages. In contrast, the epithelial tight junction components, CLDN1 and JAMA, responded to inflammatory stimulation independently of the culture passage. Our findings indicate that this HIO model contains a functional mesenchymal component, during early passages, and underline the significance of the mesenchymal cells' fitness in inflammatory and fibrotic responses. Therefore, we propose that this model is suitable for the study of epithelial-mesenchymal interactions in early passages when the mesenchymal component is active.

Organoids are self-renewing, 3D structures, consisting of different cell types, with histology and physiology features very close to the physiology of the studied organ. Specifically, human Intestinal Organoids (HIOs) develop epithelial crypts consisting of all subtypes of intestinal epithelial cells which are surrounded by mesenchymal cells. Our aim was to develop 3D HIOs from human embryonic stem cells (hESCs) and examine the expression of fibrotic and mesenchymal factors during their maturation process. Additionally, we investigated the effect of the pro-inflammatory cytokines, IL-1α and TNF-α on the expression of fibrotic and inflammatory mediators in HIOs. The human ESC line (H1) was cultured and then differentiated towards HIOs using commercially available kit. HIOs were characterized by immunofluorescence in all differentiation stages. In order to examine their maturation process, we compared the mRNA expression of fibrotic and mesenchymal markers from passages 1–10. In order to examine their functionality, HIOs from different passages were stimulated with 5ng/ml IL-1α and 50ng/ml TNF-α for 12 hours, total RNA was collected and the fibrotic and inflammatory mRNA expression was examined. The mRNA transcripts of CD90, collagen type I, III, fibronectin, CXCL8, CXCL10 and CXCL11 were measured by reverse transcription quantitative PCR. HIOs were successfully developed as they were stained positive for all tested markers throughout their developmental process. Regarding their maturation process, we observed high expression of CD90, collagen type I, type III and fibronectin that was gradually decreased during passages. As for the fibrotic and inflammatory responses from HIOs, we found that the IL-1α and TNF-α stimulation resulted in statistically significant upregulation of the fibrotic factors, fibronectin, collagen type I and type III in culture passages 2 and 4, but had no effect in culture passages 8 and 10. Similarly, IL-1α and TNF-α stimulation led to the statistically significant induction of the inflammatory chemokines CXCL8, CXCL10 and CXCL11 in culture passages 2 and 4, while no effect was observed in culture passages 8 and 10. Our findings indicate that HIOs contain a functional mesenchymal component that is gradually diminished during passages. Inflammatory and fibrotic responses of HIOs seem to depend on the fitness of their mesenchyme. IBD studies using HIOs as in vitro models should be performed on early passages, when HIO’s mesenchymal component is still functional.

Idiopathic pulmonary fibrosis is a chronic, progressive parenchymal lung disease that results in fibrogenesis and the conditioned medium from adipose-derived mesenchymal stem cells (CM-ADSCs) has been shown to be efficacious in pulmonary fibrosis animal models. The aim of the present study is to evaluate the effect of CM-ADSCs on lung inflammation and fibrosis in a Bleomycin (BLM)-induced pulmonary fibrosis model. CM-ADSCs safety and toxicity were evaluated in Sprague Dawley rats and no adverse effects were observed. Six-week-old female C57BL/6J mice were employed in the BLM-induced pulmonary fibrosis model and were divided into four groups: Group 1 (Sham): animals were kept without BLM and treatment, Group 2 (Control): BLM with vehicle DMEM, Group 3: 10 μg/kg CM-ADSCs and Group 4: 100 μg/kg CM-ADSCs. Body weight, fibrosis and inflammation histological analyses, mRNA and protein pro-inflammatory cytokine, and total hydroxyproline content calculation were performed in all groups upon sacrifice. The 100 μg/kg CM-ADSCs showed a significant increase in mean body weight compared to Controls. CM-ADSCs doses resulted in the amelioration of fibrosis, as seen by Masson's Trichrome-staining, Ashcroft scoring, and Sirius red-staining. Compared to Controls, inflammation was also significantly reduced in CM-ADSCs-treated mice, with reduced F4/80 macrophage antigen staining, TNF-α mRNA and IL-6 and IL-10 protein levels. Total hydroxyproline content was found significantly reduced in both groups of CM-ADSCs-treated mice. Overall, our study shows that the CM-ADSCs is safe and efficient against pulmonary fibrosis, as it significantly reduced inflammation and fibrosis, with the larger dose of 100 μg/kg CM-ADSCs being the most efficient one.

Regenerative medicine is a novel scientific field that employs the use of stem cells as cell-based therapy for the regeneration and functional restoration of damaged tissues and organs. Stem cells bear characteristics such as the capacity for self-renewal and differentiation towards specific lineages and, therefore, serve as a backup reservoir in case of tissue injuries. Therapeutically, they can be autologously or allogeneically transplanted for tissue regeneration; however, allogeneic stem cell transplantation can provoke host immune responses leading to a host-versus-transplant reaction. A probable solution to this problem is stem cell encapsulation, a technique that utilizes various biomaterials for the creation of a semi-permeable membrane that encases the stem cells. Stem cell encapsulation can be accomplished by employing a great variety of natural and/or synthetic hydrogels and offers many benefits in regenerative medicine, including protection from the host's immune system and mechanical stress, improved cell viability, proliferation and differentiation, cryopreservation and controlled and continuous delivery of the stem-cell-secreted therapeutic agents. Here, in this review, we report and discuss almost all natural and synthetic hydrogels used in stem cell encapsulation, along with the benefits that these materials, alone or in combination, could offer to cell therapy through functional cell encapsulation.

Obesity is a medical condition in which excess body fat may have a negative effect on health and lifestyle, and it is becoming an increasing problem within modern society. Leptin is the key protein that regulates body energy balance by inhibiting hunger, and it could potentially be used in treatment of obesity and overweight. Here, we applied our own Resonant Recognition Model, which is capable of analyzing the selectivity of any protein–receptor interaction on an example of leptin–leptin receptor. We have identified a specific characteristic parameter for leptin activity through the leptin receptor, and this parameter could be used in development of new treatments for obesity.

Differentiation of stem cells into different tissues is a promising approach to treat a large number of diseases, as well as for tissue transplantation and repair. It has been shown that parathyroid hormone, similarly to stromal self-derived factor, and the radiation of specific electromagnetic frequencies of blue and green light, can encourage stem cell differentiation into osteoblasts. Here, we analysed parathyroid hormone, its receptor and stromal self-derived factor using the Resonant Recognition Model, which proposes that protein function is based on specific frequencies of electromagnetic radiation within ultra-violet, visible, infra-red and far infra-red light. The purpose of this research is to predict the characteristic frequencies related to parathyroid hormone activities, particularly differentiation of stem cells into osteoblasts. We have found that the most effective wavelength for stem cell differentiation would be 502 nm, which is between 420 nm and 540 nm, already experimentally proven to be effective in stimulating osteoblast differentiation. Thus, we propose that wavelength radiation of 502 nm will be even more efficient for differentiation of stem cells into osteoblasts.

The cystic fibrosis is genetic disease characterised by build-up of thick mucus in the lungs, which causes difficulties in breathing. It is caused by mutations in CFTR protein. Here, we utilised the Resonant Recognition Model (RRM), which proposes that proteins specific activity is characterised by specific frequencies (wavelengths) of electromagnetic radiation. Using the RRM approach, we have identified the electromagnetic frequency (wavelength) characterising the healthy CFTR proteins, while the amplitude at this frequency is diminishing in mutated CFTR proteins. Thus, the identified characteristic frequency (wavelength) for heathy CFTR proteins could be proposed to be critical for healthy functioning of CFTR proteins and for differentiating between healthy and malfunctioning CFTR proteins related to cystic fibrosis. In addition, using the RRM approach we achieved the possible explanation on how specific temperature of 27-28°C can restore the healthy function in mutated CFTR proteins.

Osteoporosis is a systemic disease that affects the skeleton, causing reduction of bone density and mass, resulting in destruction of bone microstructure and increased risk of bone fractures. Since osteoporosis is a disease affecting the elderly and the aging of the world’s population is constantly increasing, it is expected that the incidence of osteoporosis and its financial burden on the insurance systems will increase continuously and there is a need for more understanding this condition in order to prevent and/or treat it. At present, available drug therapy for osteoporosis primarily targets the inhibition of bone resorption and agents that promote bone mineralization, designed to slow disease progression. Safe and predictable pharmaceutical means to increase bone formation have been elusive. Stem cell therapy of osteoporosis, as a therapeutic strategy, offers the promise of an increase in osteoblast differentiation and thus reversing the shift towards bone resorption in osteoporosis. This review is focused on the current views regarding the implication of the stem cells in the cellular and physiologic mechanisms of osteoporosis and discusses data obtained from stem cell-based therapies of osteoporosis in experimental animal models and the possibility of their future application in clinical trials.

Background: Peritoneal adhesions, organized as fibrous bands after abdominal surgery, are related with considerable morbidity and repeated hospitalization. Phospholipids, natural constituents of the peritoneal fluid, seem to display excellent antiadhesive properties. The aim of this study was to investigate whether intraperitoneal application of phospholipids is capable of reducing postoperative adhesions and the possible underlying mechanisms.Materials and methods: Twenty male Wistar rats were subjected to amidline laparotomy and a standard peritoneal and cecum abrasion trauma. Before laparotomy closure, a bolus of 3 mL of phospholipids (12 mg/mL) or NaCl (placebo) was given intraperitoneally. Seven days later, the quality and the quantity of adhesions, as well as serum proinflammatory and/or profibrotic mediators, were blindly assessed. Human colonic subepithelial myofibroblasts were isolated from normal controls and cultured with transforming growth factor-beta 1 (TGF beta 1, 5 ng/mL) in the presence of phospholipids (30-300 mg/mL). Collagen production in culture supernatants and migratory activity of myofibroblasts were also assessed.Results: Phospholipids reduced intra-abdominal adhesions (P < 0.001), with respect to their intensity and area, and serum levels of cytokines (interleukin 1 beta, interleukin 6, platelet-derived growth factor-1, and TGF beta 1) compared with placebo-treated rats. Stimulation of myofibroblasts with TGFb1 significantly increased (P < 0.001) the basic collagen production. The presence of phospholipids significantly reduced (P < 0.001) both the TGF beta 1 induced and the basic collagen production. Using a wound healing assay, phospholipids were found to reduce the basic and the TGF beta 1-induced migration of myofibroblasts in a concentration-dependent manner.Conclusions: Intraperitoneal phospholipids might be involved in the prevention of postoperative adhesions formation via the reduction of proinflammatory and/or profibrotic mediators and by inhibiting fibrogenic properties of mesenchymal cells. (C) 2015 Elsevier Inc. All rights reserved.