Mesenchymal Stem Cell Plasticity: What Role Do Culture Conditions and Substrates Play in Shaping Biomechanical Signatures?

Cell functionality, driven by remarkable plasticity, is strongly influenced by mechanical forces that regulate mesenchymal stem cell (MSC) fate. This study explores the biomechanical properties of jaw periosteal cells (JPCs) and induced mesenchymal stem cells (iMSCs) under different culture conditions. We cultured both JPCs and iMSCs (n = 3) under normoxic and hypoxic environments, with and without osteogenic differentiation, and on laminin- or gelatin-coated substrates.

PIEZO1-mediated calcium influx transiently alters nuclear mechanical properties via actin remodeling in chondrocytes.

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca ion channel, has been shown to be important in sensing mechanical stress, however its signal transduction pathway is not thoroughly understood.

Cracking the Pericellular Matrix Code: Exploring how MMP-2, -3, and -7 influence matrix breakdown and biomechanical properties.

Introduction: The intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.

Biomarkers for hypertrophic chondrocyte differentiation are associated with spatial cellular organisation and suggest endochondral ossification-like processes in osteoarthritic cartilage: An exploratory study.

Background: In healthy articular cartilage, chondrocytes are found along arcades of collagen fibers as Single Strings. With onset of cartilage degeneration this pattern changes to Double Strings. In the course of osteoarthritis Small Clusters, and finally Big Clusters form.

Proteolysis of the pericellular matrix: Pinpointing the role and involvement of matrix metalloproteinases in early osteoarthritic remodeling.

The pericellular matrix (PCM) serves a critical role in signal transduction and mechanoprotection in chondrocytes. Osteoarthritis (OA) leads to a gradual deterioration of the cartilage, marked by a shift in the spatial arrangement of chondrocytes from initially isolated strands to large cell clusters in end-stage degeneration. These changes coincide with progressive enzymatic breakdown of the PCM.

Reliability and Accuracy of the Outerbridge Classification in Staging of Cartilage Defects.

Objective: The decision on whether or not and how to treat a local cartilage defect is still made intraoperatively based on the visual presentation of the cartilage and findings from indentations with an arthroscopic probe. The treatment decision is then usually based on grading according to established classifications systems, which, therefore, need to have high reliability and accuracy. The aim of the present study was to evaluate the reliability and accuracy of the Outerbridge classification in staging cartilage defects.

An exploratory study of cell stiffness as a mechanical label-free biomarker across multiple musculoskeletal sarcoma cells.

Background: Cancer cells are characterized by changes in cell cytoskeletal architecture and stiffness. Despite advances in understanding the molecular mechanisms of musculoskeletal cancers, the corresponding cellular mechanical properties remain largely unexplored. The aim of this study was to investigate the changes in cellular stiffness and the associated cytoskeleton configuration alterations in various musculoskeletal cancer cells.

Biomechanical and biochemical assessment of YB-1 expression in A375 melanoma cell line: Exploratory study.

Malignant melanoma is the most lethal form of skin cancer. Y-box binding protein 1 (YB-1) plays a prominent role in mediating metastatic behavior by promoting epithelial-to-mesenchymal transition (EMT). Migratory melanoma cells exhibit two major migration modes: elongated mesenchymal or rounded amoeboid.

Changes in stiffness of the extracellular and pericellular matrix in the anulus fibrosus of lumbar intervertebral discs over the course of degeneration.

Analogous to articular cartilage, changes in spatial chondrocyte organisation have been proposed to be a strong indicator for local tissue degeneration in the intervertebral disc (IVD). While a progressive structural and functional degradation of the extracellular (ECM) and pericellular (PCM) matrix occurs in osteoarthritic cartilage, these processes have not yet been biomechanically elucidated in the IVD. We aimed to evaluate the local stiffness of the ECM and PCM in the anulus fibrosus of the IVD on the basis of local chondrocyte spatial organisation.

5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas.

Ewing sarcomas (ES) are aggressive primary bone tumors that require radical therapy. Promising low toxicity, 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) could enhance the effectiveness of conventional treatment modalities (e.g.

How osteogenic is dexamethasone?-effect of the corticosteroid on the osteogenesis, extracellular matrix, and secretion of osteoclastogenic factors of jaw periosteum-derived mesenchymal stem/stromal cells.

Dexamethasone (dexa) is commonly used to stimulate osteogenic differentiation of mesenchymal stem/stromal cells (MSCs) However, it is paradoxical that glucocorticoids (GCs) such as dexa lead to bone loss and increased fracture risk in patients undergoing glucocorticoid therapy, causing glucocorticoid-induced osteoporosis (GIOP). In a recent publication, we demonstrated that osteogenic differentiation of progenitor cells isolated from jaw periosteal tissue (JPCs) does not depend on dexa, if the medium is supplemented with human platelet lysate (hPL) instead of fetal bovine serum (FBS). This allows the conditions to be much closer to the natural situation and enables us to compare osteogenic differentiation with and without dexa.

Addressing Practical Issues in Atomic Force Microscopy-Based Micro-indentation on Human Articular Cartilage Explants.

Without a doubt, atomic force microscopy (AFM) is currently one of the most powerful and useful techniques to assess micro and even nano-cues in the biological field. However, as with any other microscopic approach, methodological challenges can arise. In particular, the characteristics of the sample, sample preparation, type of instrument, and indentation probe can lead to unwanted artifacts.

5-Aminolevulinic Acid-mediated Photodynamic Therapy on Primary Bone Tumor and Bone Metastases Cell Lines.

Bone metastases are associated with poor prognosis and low quality of life for the affected patients. Photodynamic therapy (PDT) emerges as a noninvasive therapy that can target local metastatic bone lesions. This paper presents an in vitro method to study the PDT effect in adherent cell lines.

Detecting early osteoarthritis through changes in biomechanical properties - A review of recent advances in indentation technologies in a clinical arthroscopic setup.

Osteoarthritis (OA) is a degenerative joint disease currently affecting half of all women and one-third of all men aged over 65 and it is predicted to even increase in the next decades. In the variety of causes leading to OA, the first common denominator are changes in the extracellular matrix of the cartilage. In later stages, OA affects the whole joint spreading to higher levels of tissue architecture causing irreversible functional and structural damage.

Assessment of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy on Bone Metastases: An in Vitro Study.

Bone is a frequent site of metastases, being typically associated with a short-term prognosis in affected patients. Photodynamic therapy (PDT) emerges as a promising alternative treatment for controlling malignant disease that can directly target interstitial metastatic lesions. The aim of this study was to assess the effect induced by PDT treatment on both primary (giant cell bone tumor) and human bone metastatic cancer cell lines (derived from a primary invasive ductal breast carcinoma and renal carcinoma).

Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration.

Intervertebral disc (IVD) degeneration is a leading cause of low back pain and it entails a high degree of impairment for the affected individuals. To decode disc degeneration and to be able to develop regenerative approaches a thorough understanding of the cellular biology of the IVD is essential. One aspect of this biology that still remains unanswered is the question of how cells are spatially arranged in a physiological state and during degeneration.

Intravascular Application of Labelled Cell Spheroids: An Approach for Ischemic Peripheral Artery Disease.

Mesenchymal stem cells (MSC) are known for their vascular regeneration capacity by neoangiogenesis. Even though, several delivery approaches exist, particularly in the case of intravascular delivery, only limited number of cells reach the targeted tissue and are not able to remain on site. Applicated cells exhibit poor survival accompanied with a loss of functionality.

Exploration of changes in spatial chondrocyte organisation in human osteoarthritic cartilage by means of 3D imaging.

Using two-dimensional top-down view microscopy, researchers have recently described chondrocytes as being spatially arranged in distinct patterns such as strings, double strings, and small and large clusters. Because of the seeming association of these changes with tissue degeneration, they have been proposed as an image-based biomarker for early osteoarthritis (OA) staging. The aim of our study was to investigate the spatial arrangement of chondrocytes in human articular cartilage in a 3D fashion and to evaluate the 3D changes of these patterns in the context of local tissue destruction.

Injection of Porcine Adipose Tissue-Derived Stromal Cells by a Novel Waterjet Technology.

Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology.

The intervertebral disc from embryonic development to disc degeneration: insights into spatial cellular organization.

Background Context: Low back pain is commonly attributed to intervertebral disc (IVD) degeneration. IVD resembles articular cartilage in its biochemical and cellular composition in many ways. For articular cartilage, degeneration stage-specific characteristic spatial chondrocyte patterns have recently been described.

Application of Atomic Force Microscopy to Detect Early Osteoarthritis.

Biomechanical properties of cells and tissues not only regulate their shape and function but are also crucial for maintaining their vitality. Changes in elasticity can propagate or trigger the onset of major diseases like cancer or osteoarthritis (OA). Atomic force microscopy (AFM) has emerged as a strong tool to qualitatively and quantitatively characterize the biomechanical properties of specific biological target structures on a microscopic scale, measuring forces in a range from as small as the piconewton to the micronewton.

Biochemical changes of the pericellular matrix and spatial chondrocyte organization-Two highly interconnected hallmarks of osteoarthritis.

During osteoarthritis, chondrocytes change their spatial arrangement from single to double strings, then to small and big clusters. This change in pattern has recently been established as an image-based biomarker for osteoarthritis. The pericellular matrix (PCM) appears to degrade together alongside cellular reorganization.

Assessment of biomechanical properties of the extracellular and pericellular matrix and their interconnection throughout the course of osteoarthritis.

During osteoarthritis (OA)-triggered cartilage degeneration, the chondrocytes spatially rearrange from single to double strings, and then to small and finally big clusters. Both the extracellular matrix (ECM) and the pericellular matrix (PCM) progressively degrade in osteoarthritis, changing the overall mechanical properties of the cartilage. We investigated the mechanical properties particularly elasticity of the ECM and PCM and their interconnection as a function of chondrocyte spatial organisation.

Quality Analysis of Minerals Formed by Jaw Periosteal Cells under Different Culture Conditions.

Previously, we detected a higher degree of mineralization in fetal calf serum (FCS) compared to serum-free cultured jaw periosteum derived osteoprogenitor cells (JPCs). By Raman spectroscopy, we detected an earlier formation of mineralized extracellular matrix (ECM) of higher quality under serum-free media conditions. However, mineralization potential remained too low.