Different levels of EGF, VEGF, IL-6, MCP-1, MCP-3, IP-10, Eotaxin and MIP-1α in the adipose-derived stem cell secretome in androgenetic alopecia.

Hair folliculogenesis and hair growth mediated by the secretory properties of white adipocytes may pave the way for the adipose-derived (AD) regenerative therapy for androgenetic alopecia (AGA). Quantitative and qualitative secretome profiling of AD stem cells (ADSCs) from different zones of hair growth in patients with AGA were analysed. 1-mm punch samples of adipose tissue associated with hair follicles, of three scalp areas (balding, non-balding and transition zones) and one periumbilical sample, were used for ADCS isolation. The ADCS secretome was analysed in conditioned media using a 41plex assay. Among the thirty-five signalling proteins analysed, the levels of VEGF, EGF, IL-6, Eotaxin, MCP-3, IFNγ-inducible protein-10 and MIP-1α were higher in the balding zone compared with the non-balding and periumbilical zones. In contrast, MCP-1 was the lowest in the balding zone in comparison with the other zones. The observed differences in the secretome suggest crosstalk between angiogenic and inflammatory processes underlying AGA aetiology and may prove relevant in both the diagnosis of AGA and the application of ADSC secretome for AGA treatment.

Molecular Mechanisms Underlying Pathological and Therapeutic Roles of Pericytes in Atherosclerosis.

Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a key role in the pathogenesis and development of atherosclerosis (AS). Pericytes are involved in lipid accumulation, inflammation, growth, and vascularization of the atherosclerotic plaque. Decreased pericyte coverage, endothelial and pericyte dysfunction is associated with intraplaque angiogenesis and haemorrhage, calcification and cholesterol clefts deposition. At the same time, pericytes can be used as a novel therapeutic target to promote vessel maturity and stability, thus reducing plaque vulnerability. Finally, we discuss recent studies exploring effective AS treatments with pericyte-mediated anti-atherosclerotic, anti-inflammatory and anti-apoptotic effects.

Shambhala: a platform-agnostic data harmonizer for gene expression data.

BACKGROUND: Harmonization techniques make different gene expression profiles and their sets compatible and ready for comparisons. Here we present a new bioinformatic tool termed Shambhala for harmonization of multiple human gene expression datasets obtained using different experimental methods and platforms of microarray hybridization and RNA sequencing. RESULTS: Unlike previously published methods enabling good quality data harmonization for only two datasets, Shambhala allows conversion of multiple datasets into the universal form suitable for further comparisons. Shambhala harmonization is based on the calibration of gene expression profiles using the auxiliary standardization dataset. Each profile is transformed to make it similar to the output of microarray hybridization platform Affymetrix Human Gene. This platform was chosen because it has the biggest number of human gene expression profiles deposited in public databases. We evaluated Shambhala ability to retain biologically important features after harmonization. The same four biological samples taken in multiple replicates were profiled independently using three and four different experimental platforms, respectively, then Shambhala-harmonized and investigated by hierarchical clustering. CONCLUSION: Our results showed that unlike other frequently used methods: quantile normalization and DESeq/DESeq2 normalization, Shambhala harmonization was the only method supporting sample-specific and platform-independent biologically meaningful clustering for the data obtained from multiple experimental platforms.

Diagnostics of atherosclerosis: Overview of the existing methods.

Atherosclerosis was and remains an extremely common and serious health problem. Since the elderly are most at risk of cardiovascular risk, and the average life expectancy is increasing, the spread of atherosclerosis and its consequences increases as well. One of the features of atherosclerosis is its asymptomaticity. This factor makes it difficult to make a timely diagnosis. This entails the lack of timely treatment and even prevention. To date, in the arsenal of physicians, there is only a limited set of methods to suspect and fully diagnose atherosclerosis. In this review, we have tried to briefly describe the most common and effective methods for diagnosing atherosclerosis.

Proprotein Convertase Subtilisin/Kexin 9 as a Modifier of Lipid Metabolism in Atherosclerosis.

Despite being the most common treatment strategy in the management of atherosclerosis and subsequent cardiovascular disease, classical statin therapy has certain disadvantages, including numerous side effects. In addition, a regimen with daily administration of the drug is hard to comply with. Thus, there is a need for modern and more efficient therapeutic strategies in CVD treatment. There is extensive evidence indicating that PCSK9 promotes atherogenesis through a variety of mechanisms. Thus, new treatment methods can be developed that prevent or alleviate atherosclerotic cardiovascular disease by targeting PCSK9. Comprehensive understanding of its atherogenic properties is a necessary precondition for the establishment of new therapeutic strategies. In this review, we will summarize the available data on the role of PCSK9 in the development and progression of atherosclerosis. In the last section, we will consider existing PCSK9 inhibitors.

The Role of Pericytes in Regulation of Innate and Adaptive Immunity.

Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise recent data regarding pericytes' response to different pro-inflammatory stimuli and their involvement in innate immune responses through expression of pattern-recognition receptors. Moreover, pericytes express various adhesion molecules, thus regulating trafficking of immune cells across vessel walls. Additionally, the role of pericytes in modulation of adaptive immunity is discussed. Finally, recent reports have suggested that the interaction with cancer cells evokes immunosuppression function in pericytes, thus facilitating immune evasion and facilitating cancer proliferation and metastasis. However, such complex and multi-faceted cross-talks of pericytes with immune cells also suggest a number of potential pericyte-based therapeutic methods and techniques for cancer immunotherapy and treatment of autoimmune and auto-inflammatory disorders.

HDL-Based Therapy: Vascular Protection at All Stages.

It is known that lipid metabolism disorders are involved in a wide range of pathologies. These pathologies include cardiovascular, metabolic, neurodegenerative diseases, and even cancer. All these diseases lead to serious health consequences, which makes it impossible to ignore them. Unfortunately, these diseases most often have a complex pathogenesis, which makes it difficult to study them and, in particular, diagnose and treat them. HDL is an important part of lipid metabolism, performing many functions under normal conditions. One of such functions is the maintaining of the reverse cholesterol transport. These functions are also implicated in pathology development. Thus, HDL contributes to vascular protection, which has been demonstrated in various conditions: Alzheimer's disease, atherosclerosis, etc. Many studies have shown that serum levels of HDL cholesterol correlate negatively with CV risk. With these data, HDL-C is a promising therapeutic target. In this manuscript, we reviewed HDL-based therapeutic strategies that are currently being used or may be developed soon.

Hypotheses on Atherogenesis Triggering: Does the Infectious Nature of Atherosclerosis Development Have a Substruction?

Since the end of the 20th century, it has been clear that atherosclerosis is an inflammatory disease. However, the main triggering mechanism of the inflammatory process in the vascular walls is still unclear. To date, many different hypotheses have been put forward to explain the causes of atherogenesis, and all of them are supported by strong evidence. Among the main causes of atherosclerosis, which underlies these hypotheses, the following can be mentioned: lipoprotein modification, oxidative transformation, shear stress, endothelial dysfunction, free radicals' action, homocysteinemia, diabetes mellitus, and decreased nitric oxide level. One of the latest hypotheses concerns the infectious nature of atherogenesis. The currently available data indicate that pathogen-associated molecular patterns from bacteria or viruses may be an etiological factor in atherosclerosis. This paper is devoted to the analysis of existing hypotheses for atherogenesis triggering, and special attention is paid to the contribution of bacterial and viral infections to the pathogenesis of atherosclerosis and cardiovascular disease.

Emerging role of pericytes in therapy of cardiovascular diseases.

Pericytes are mural vascular cells covering microvascular capillaries, where they contribute to the formation, maturation, maintenance, stabilisation and remodelling of vasculature. They actively interact and communicate with other cells to maintain the capillary structural integrity, vascular permeability and blood flow. Pericytes are crucial participants in the physiological and pathological processes of cardiovascular disease. In this review, we summarise recent data regarding pericyte metabolism, trans-differentiation, angiogenesis and immunomodulation in connection with different cardiovascular pathologies. Further, we discuss an application of pericytes as a new cell therapy approach to treat coronary artery disease, congenital heart disease, atherosclerotic plaques calcification and calcific valvular heart disease in different in vivo animal models and in vitro studies. Also, we discuss different methods and pharmacological therapies for CVDs treatment with pericyte-mediated effects. Finally, we present a comprehensive overview of the role of pericytes in CVDs and as a pharmacological target for different novel drugs and techniques and highlight the potential application of pericytes to treat CVDs.

Myogenic potential of human alveolar mucosa derived cells.

Difficulties related to the obtainment of stem/progenitor cells from skeletal muscle tissue make the search for new sources of myogenic cells highly relevant. Alveolar mucosa might be considered as a perspective candidate due to availability and high proliferative capacity of its cells. Human alveolar mucosa cells (AMC) were obtained from gingival biopsy samples collected from 10 healthy donors and cultured up to 10 passages. AMC matched the generally accepted multipotent mesenchymal stromal cells criteria and possess population doubling time, caryotype and immunophenotype stability during long-term cultivation. The single myogenic induction of primary cell cultures resulted in differentiation of AMC into multinucleated myotubes. The myogenic differentiation was associated with expression of skeletal muscle markers: skeletal myosin, skeletal actin, myogenin and MyoD1. Efficiency of myogenic differentiation in AMC cultures was similar to that in skeletal muscle cells. Furthermore, some of differentiated myotubes exhibited contractions in vitro. Our data confirms the sufficiently high myogenic potential and proliferative capacity of AMC and their ability to maintain in vitro proliferation-competent myogenic precursor cells regardless of the passage number.

Octacalcium phosphate ceramics combined with gingiva-derived stromal cells for engineered functional bone grafts.

Biocompatible ceramic fillers are capable of sustaining bone formation in the proper environment. The major drawback of these scaffolding materials is the absence of osteoinductivity. To overcome this limitation, bioengineered scaffolds combine osteoconductive components (biomaterials) with osteogenic features such as cells and growth factors. The bone marrow mesenchymal stromal cells (BMMSCs) and the ß-tricalcium phosphate (ß-TCP) are well-known and characterized in this regard. The present study was conducted to compare the properties of novel octacalcium phosphate ceramic (OCP) granules with ß-TCP (Cerasorb(®)), gingiva-derived mesenchymal stromal cells (GMSCs) properties with the BMMSCs and osteogenic and angiogenic properties of a bioengineered composite based on OCP granules and the GMSCs. This study demonstrates that GMSCs and BMMSСs have a similar osteogenic capacity. The usage of OCP ceramic granules in combination with BMMSCs/GMSCs significantly affects the osteo- and angiogenesis in bone grafts of ectopic models.

Bioceramics composed of octacalcium phosphate demonstrate enhanced biological behavior.

Bioceramics are used to treat bone defects but in general do not induce formation of new bone, which is essential for regeneration process. Many aspects related to bioceramics synthesis, properties and biological response that are still unknown and, there is a great need for further development. In the most recent research efforts were aimed on creation of materials from biological precursors of apatite formation in humans. One possible precursor is octacalcium phosphate (OCP), which is believed to not only exhibit osteoconductivity but possess osteoinductive quality, the ability to induce bone formation. Here we propose a relatively simple route for OCP ceramics preparation with a specifically designed microstructure. Comprehensive study for OCP ceramics including biodegradation, osteogenic properties in ortopic and heterotopic models and limited clinical trials were performed that demonstrated enhanced biological behavior. Our results provide a possible new concept for the clinical applications of OCP ceramics.