Clinical and functional characterization of p.Gly444Ser variant: From a fetal phenotype to a previously undisclosed postnatal phenotype.

gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.

Mesenchymal Stromal Cells Laden in Hydrogels for Osteoarthritis Cartilage Regeneration: A Systematic Review from In Vitro Studies to Clinical Applications.

This systematic review is focused on the main characteristics of the hydrogels used for embedding the mesenchymal stromal cells (MSCs) in in vitro/ex vivo studies, in vivo OA models and clinical trials for favoring cartilage regeneration in osteoarthritis (OA). PubMED and Embase databases were used to select the papers that were submitted to a public reference manager Rayyan Systematic Review Screening Software. A total of 42 studies were considered eligible: 25 articles concerned in vitro studies, 2 in vitro and ex vivo ones, 5 in vitro and in vivo ones, 8 in vivo ones and 2 clinical trials.

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel.

Autophagy is a cellular process that contributes to the maintenance of cell homeostasis through the activation of a specific path, by providing the necessary factors in stressful and physiological situations. Autophagy plays a specific role in chondrocyte differentiation; therefore, we aimed to analyze this process in adipose-derived mesenchymal stromal cells (ASCs) laden in three-dimensional (3D) hydrogel. We analyzed chondrogenic and autophagic markers using molecular biology, immunohistochemistry, and electron microscopy.

Primers for the Adhesion of Gellan Gum-Based Hydrogels to the Cartilage: A Comparative Study.

A stable adhesion to the cartilage is a crucial requisite for hydrogels used for cartilage regeneration. Indeed, a weak interface between the tissue and the implanted material may produce a premature detachment and thus the failure of the regeneration processes. Fibrin glue, cellulose nanofibers and catecholamines have been proposed in the state-of-the-art as primers to improve the adhesion.

RGD-Functionalized Hydrogel Supports the Chondrogenic Commitment of Adipose Mesenchymal Stromal Cells.

Articular cartilage is known to have limited intrinsic self-healing capacity when a defect or a degeneration process occurs. Hydrogels represent promising biomaterials for cell encapsulation and injection in cartilage defects by creating an environment that mimics the cartilage extracellular matrix. The aim of this study is the analysis of two different concentrations (1:1 and 1:2) of VitroGel (VG) hydrogels without (VG-3D) and with arginine-glycine-aspartic acid (RGD) motifs, (VG-RGD), verifying their ability to support chondrogenic differentiation of encapsulated human adipose mesenchymal stromal cells (hASCs).

Mesenchymal stromal cells from a progressive pseudorheumatoid dysplasia patient show altered osteogenic differentiation.

Background: Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory skeletal disease with childhood onset and is characterized by a progressive chondropathy in multiple joints, and skeletal abnormalities. To date, the etiopathological relationship between biological modification occurring in PPRD and genetic mutation remains an open issue, partially due to the limited availability of biological samples obtained from PPRD patients for experimental studies.

Case Presentation: We describe the clinical features of a PPRD patient and experimental results obtained from the biological characterization of PPRD mesenchymal stromal cells (MSCs) and osteoblasts (OBs) compared to normal cell populations.

Bone Regeneration Improves with Mesenchymal Stem Cell Derived Extracellular Vesicles (EVs) Combined with Scaffolds: A Systematic Review.

Scaffolds associated with mesenchymal stem cell (MSC) derivatives, such as extracellular vesicles (EVs), represent interesting carriers for bone regeneration. This systematic review aims to analyze in vitro and in vivo studies that report the effects of EVs combined with scaffolds in bone regeneration. A methodical review of the literature was performed from PubMed and Embase from 2012 to 2020.

Modeling and Fabrication of Silk Fibroin-Gelatin-Based Constructs Using Extrusion-Based Three-Dimensional Bioprinting.

Robotic dispensing-based 3D bioprinting represents one of the most powerful technologies to develop hydrogel-based 3D constructs with enormous potential in the field of regenerative medicine. The optimization of hydrogel printing parameters, proper geometry and internal architecture of the constructs, and good cell viability during the bioprinting process are the essential requirements. In this paper, an analytical model based on the hydrogel rheological properties was developed to predict the extruded filament width in order to maximize the printed structure's fidelity to the design.

Impact of Isolation Procedures on the Development of a Preclinical Synovial Fibroblasts/Macrophages in an In Vitro Model of Osteoarthritis.

There is a lack ofin vitromodels able to properly represent osteoarthritis (OA) synovial tissue (ST). We aimed to characterize OA ST and to investigate whether a mechanical or enzymatic digestion procedures influence synovial cell functional heterogeneity in vitro. Procedures using mechanical nondigested fragments (NDF), synovial digested fragments (SDF), and filtrated synovial digested cells (SDC) were compared.

Osteoarthritic Milieu Affects Adipose-Derived Mesenchymal Stromal Cells.

The objective of this study was to define the effects of osteoarthritic (OA) milieu on good manufactured practice-adipose-derived mesenchymal stromal cells (GMP-ASC) that are commonly utilized in cell therapies. Two different OA milieu: OA synovial fluid (SF) and OA-conditioned medium (CM) from synoviocytes were used to treat GMP-ASC both in normoxia or hypoxia. GMP-ASC were tested for cell migration, proliferation, cytokine receptors expression (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, CCR1, CCR2, CCR3, CCR5, IL6R), and cytokines (CXCL8/IL8, CXCL10/IP10, CXCL12/SDF-1, CCL2/MCP1, CCL3/MIP1α, CCL4/MIP1β, CCL5/RANTES, IL6) release.

Specific concentration of hyaluronan amide derivative induces osteogenic mineralization of human mesenchymal stromal cells: Evidence of RUNX2 and COL1A1 genes modulation.

Hyaluronic acid (HA) is an ideal material for tissue regeneration. The aim of this study was to investigate whether a hyaluronan amide derivative (HAD) can enhance the mineralization of human mesenchymal stem cells (hMSCs). Osteogenically induced hMSCs cultured with or without HAD at different concentrations (0.

Chitosan-based scaffold counteracts hypertrophic and fibrotic markers in chondrogenic differentiated mesenchymal stromal cells.

Cartilage tissue engineering remains problematic because no systems are able to induce signals that contribute to native cartilage structure formation. Therefore, we tested the potentiality of gelatin-polyethylene glycol scaffolds containing three different concentrations of chitosan (CH; 0%, 8%, and 16%) on chondrogenic differentiation of human platelet lysate-expanded human bone marrow mesenchymal stromal cells (hBM-MSCs). Typical chondrogenic (SOX9, collagen type 2, and aggrecan), hypertrophic (collagen type 10), and fibrotic (collagen type 1) markers were evaluated at gene and protein level at Days 1, 28, and 48.

Rational Design and Development of Anisotropic and Mechanically Strong Gelatin-Based Stress Relaxing Hydrogels for Osteogenic/Chondrogenic Differentiation.

Rational design and development of tailorable simple synthesis process remains a centerpiece of investigational efforts toward engineering advanced hydrogels. In this study, a green and scalable synthesis approach is developed to formulate a set of gelatin-based macroporous hybrid hydrogels. This approach consists of four sequential steps starting from liquid-phase pre-crosslinking/grafting, unidirectional freezing, freeze-drying, and finally post-curing process.

Investigating the Role of Sustained Calcium Release in Silk-Gelatin-Based Three-Dimensional Bioprinted Constructs for Enhancing the Osteogenic Differentiation of Human Bone Marrow Derived Mesenchymal Stromal Cells.

Scaffold-based bone tissue engineering strategies fail to meet the clinical need to fabricate patient-specific and defect shape-specific, anatomically relevant load-bearing bone constructs. 3D bioprinting strategies are gaining major interest as a potential alternative, but design of a specific bioink is still a major challenge that can modulate key signaling pathways to induce osteogenic differentiation of progenitor cells, as well as offer appropriate microenvironment to augment mineralization. In the present study, we developed silk fibroin protein and gelatin-based conjugated bioink, which showed localized presence and sustained release of calcium.

Cartilage and Bone Serum Biomarkers as Novel Tools for Monitoring Knee Osteochondritis Dissecans Treated with Osteochondral Scaffold.

Knee osteochondritis dissecans (OCD) is a focal disease of the joint characterized by modifications of bone and cartilage tissues. Biomimetic osteochondral scaffolds are used to restore these tissues. The aim of this prognostic prospective cohort study was to evaluate serum biomarkers of cartilage (fragments or propeptide of type II collagen: CTXII, C2C, and CPII) and bone (tartrate-resistant acid phosphatase (TRAP) 5b and osteocalcin (OC)) turnover during follow-up of patients treated with an osteochondral scaffold, to identify which were related to healing outcome and clinical score.

Effect of microfragmented adipose tissue on osteoarthritic synovial macrophage factors.

Cell-based therapies using adipose-derived mesenchymal stromal cells (ADMSCs) have shown promising results for the treatment of osteoarthritis (OA). In fact, ADMSCs are now indicated as one of the most powerful cell sources through their immunomodulatory and anti-inflammatory activities. Recently, an innovative one-step closed device was developed to obtain microfragmented adipose tissue (MF) to avoid the need for good manufacturing practices for ADMSCs expansion while maintaining their regenerative potential.

Clinical and Biological Signature of Osteochondritis Dissecans in a Cross-Sectional Study.

The healing potential of knee osteochondritis dissecans (OCD) focal lesions is not well defined. We performed a cross-sectional study correlating local and systemic biological characteristics with the patients' characteristics. We evaluated both local tissue markers (CD34, CD146, CD166, and tartrate-resistant acid phosphatase (TRAP)) and systemic serum biomarkers (fragments or propeptide of type II collagen: C2C, CTX-II, CPII, and TRAP5b) on histologically scored osteochondral fragments or serum from OCD patients.

Immunoelectron microscopic localization of Collagen type XV during human mesenchymal stem cells mineralization.

Unlabelled: Purpose/Aim of the study. Collagen type XV (ColXV) was identified, in our previews studies, as a novel component of bone extracellular matrix. The present study aims to investigate ColXV localization during mineralization of osteodifferentiated human mesenchymal stem cells (hMSCs).

Focal Defects of the Knee Articular Surface: Evidence of a Regenerative Potential Pattern in Osteochondritis Dissecans and Degenerative Lesions.

The surgical treatment of knee articular focal lesions may offer heterogeneous clinical results. Osteochondritis dissecans (OCD) lesions showed to heal better than degenerative lesions (DL) but the underlying biological reasons are unknown. We evaluated the basal histological and immunohistochemical characteristics of these lesions analyzing a series of osteochondral fragments from young patients with similar age but presenting different etiology.

Collagen type XV and the 'osteogenic status'.

We have previously demonstrated that collagen type XV (ColXV) is a novel bone extracellular matrix (ECM) protein. It is well known that the complex mixture of multiple components present in ECM can help both to maintain stemness or to promote differentiation of stromal cells following change in qualitative characteristics or concentrations. We investigated the possible correlation between ColXV expression and mineral matrix deposition by human mesenchymal stromal cells (hMSCs) with different osteogenic potential and by osteoblasts (hOBs) that are able to grow in culture medium with or without calcium.

Distinctive expression pattern of cystathionine-β-synthase and cystathionine-γ-lyase identifies mesenchymal stromal cells transition to mineralizing osteoblasts.

Mesenchymal stromal cells (MSCs) are key players in the repair or regeneration of the damaged bone tissue. However, heterogeneity exists between MSCs derived from different donors in their bone formation ability both in vitro and in vivo. The identification of markers defining MSCs with different functional phenotypes is fundamental to maximize their clinical potential.

Age-independent effects of hyaluronan amide derivative and growth hormone on human osteoarthritic chondrocytes.

Aim: Increased age is the most prominent risk factor for the initiation and progression of osteoarthritis (OA). The effects of human growth hormone (hGH) combined or not with hyaluronan amide derivative (HAD) were evaluated on human OA chondrocytes, to define their biological action and potentiality in OA treatment.

Material And Methods: Cell viability, metabolic activity, gene expression and factors released were tested at different time points on chondrocytes treated with different concentrations of hGH (0.