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The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue

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The extracellular matrix at a glance

Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence tumour and stromal cell properties, such as proliferation and motility. Originally thought of as independent contributors to metastatic spread, recent studies have established a direct link between hypoxia and the composition and the organization of the ECM, which suggests a new model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome.

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Hypoxia and the extracellular matrix: drivers of tumour metastasis

Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes. Recent studies revealed that human placental membranes are a rich source of MSCs for tissue regeneration and repair. This review provides a concise summary of current knowledge of biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role MSCs have in each phase of the wound-healing process. In addition, characterization of MSCs containing skin substitutes is described, demonstrating the presence of key growth factors and cytokines uniquely suited to aid in wound repair.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.5966/sctm.2011-0018

Concise Review: Role of Mesenchymal Stem Cells in Wound Repair

Advanced Therapeutic Dressings for Effective Wound Healing—A Review

Recent advances on antimicrobial wound dressing: A review.

Wound healing remains a challenging clinical problem and correct, efficient wound management is essential. Much effort has been focused on wound care with an emphasis on new therapeutic approaches and the development of technologies for acute and chronic wound management. Wound healing involves multiple cell populations, the extracellular matrix and the action of soluble mediators such as growth factors and cytokines. Although the process of healing is continuous, it may be arbitrarily divided into four phases: (i) coagulation and haemostasis; (ii) inflammation; (iii) proliferation; and (iv) wound remodelling with scar tissue formation. The correct approach to wound management may effectively influence the clinical outcome. This review discusses wound classification, the physiology of the wound healing process and the methods used in wound management.

https://journals.sagepub.com/doi/pdf/10.1177/147323000903700531

The wound healing process: an overview of the cellular and molecular mechanisms.

Mesenchymal stem cells (MSCs) represent the basis of novel clinical concepts in cellular therapy and tissue regeneration. Therefore, the isolation of MSCs from various tissues has become an important endeavour for stem cell biobanking and the development of regenerative therapies. Paravertebral adipose tissue is readily exposed during spinal procedures in children and could be a viable source of stem cells for therapeutic applications. Here, we describe the first case of MSCs isolated from paravertebral adipose tissue (PV-ADMSCs), obtained during a routine spinal surgery on a child. Using quantitative real-time PCR and flow cytometry, we show that PV-ADMSCs have different levels of stem marker expression compared to the MSCs from other sources while having the highest proliferation rate. Furthermore, we evaluate the multipotency of PV-ADMSCs by the three-lineage (adipogenic, osteogenic and chondrogenic) differentiation and compare it to the multipotency of MSCs from other sources. It was found that the PV-ADMSCs have a strong osteogenic potential in particular. Taken together, our data indicate that PV-ADMSCs meet the criteria for successful cell therapy, defined by the International Society for Cellular Therapy (ISCT), and thus, could provide a source of MSCs that is relatively easy to isolate and expand in culture. Due to their strong osteogenic potential, these cells provide a promising basis, especially for orthopaedic applications.

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Mesenchymal Stem Cells Isolated from Paediatric Paravertebral Adipose Tissue Show Strong Osteogenic Potential

Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is known that infection with SARS-CoV-2 can lead to various autoimmune and autoinflammatory diseases. There are few reports in the literature on the association between SARS-CoV-2 and autoimmune diseases, and the number of reports has been increasing since 2020. Autoimmune diseases and SARS-CoV-2 infections are intertwined in several ways. Both conditions lead to immune-mediated tissue damage, the immune response is accompanied by the increased secretion of inflammatory cytokines and both conditions can be treated using immunomodulatory drugs. Patients with certain autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, cardiac sarcoidosis, idiopathic pulmonary fibrosis, autoimmune hepatitis, multiple sclerosis and others, are more susceptible to SARS-CoV-2 infection, either because of the active autoimmune disease or because of the medications used to treat it. Conversely, SARS-CoV-2 infection can also cause certain autoimmune diseases. In this paper, we describe the development of autoimmune diseases after COVID-19 and the recovery from COVID-19 in people with autoimmune diseases.

https://www.mdpi.com/2075-1729/12/11/1918/pdf?version=1668995432

A Review Pertaining to SARS-CoV-2 and Autoimmune Diseases: What Is the Connection?

Background: Degenerative disc disease is a progressive and chronic disorder with many open questions regarding its pathomorphological mechanisms. In related studies, in vitro organ culture systems are becoming increasingly essential as a replacement option for laboratory animals. Live disc cells are highly appealing to study the possible mechanisms of intervertebral disc (IVD) degeneration. To study the degenerative processes of the endplate chondrocytes in vitro, we established a relatively quick and easy protocol for isolating human chondrocytes from the vertebral endplates. Methods: The fragments of human lumbar endplates following lumbar fusion were collected, cut, ground and partially digested with collagenase I in Advanced DMEM/F12 with 5% foetal bovine serum. The sediment was harvested, and cells were seeded in suspension, supplemented with special media containing high nutrient levels. Morphology was determined with phalloidin staining and the characterisation for collagen I, collagen II and aggrecan with immunostaining. Results: The isolated cells retained viability in appropriate laboratory conditions and proliferated quickly. The confluent culture was obtained after 14 days. Six to 8 h after seeding, attachments were observed, and proliferation of the isolated cells followed after 12 h. The cartilaginous endplate chondrocytes were stable with a viability of up to 95%. Pheno- and geno-typic analysis showed chondrocyte-specific expression, which decreased with passages. Conclusions: The reported cell isolation process is simple, economical and quick, allowing establishment of a viable long-term cell culture. The availability of a vertebral endplate cell model will permit the study of cell properties, biochemical aspects, the potential of therapeutic candidates for the treatment of disc degeneration, and toxicology studies in a well-controlled environment.

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The Endplate Role in Degenerative Disc Disease Research: The Isolation of Human Chondrocytes from Vertebral Endplate—An Optimised Protocol

The blood-brain barrier (BBB) functions as a highly selective border of endothelial cells, protecting the central nervous system from potentially harmful substances by selectively controlling the entry of cells and molecules, including components of the immune system. To study the BBB properties, find suitable therapies, and identify new drug targets, there is a need to develop representative in vitro BBB models. In this article, we describe the astrocyte roles in the BBB functioning and human in vitro BBB models.

https://www.bjbms.org/ojs/index.php/bjbms/article/download/6943/2487

Tomaz Velnar

Papers

The wound healing process: an overview of the cellular and molecular mechanisms.

Mesenchymal Stem Cells Isolated from Paediatric Paravertebral Adipose Tissue Show Strong Osteogenic Potential

A Review Pertaining to SARS-CoV-2 and Autoimmune Diseases: What Is the Connection?

The Endplate Role in Degenerative Disc Disease Research: The Isolation of Human Chondrocytes from Vertebral Endplate—An Optimised Protocol

Astrocytes and human artificial blood-brain barrier models