Background: Mesenchymal stem/stromal cells (MSCs) can replenish the aged cells of the musculoskeletal system in adult life. Stem cell exhaustion and decrease in their regenerative potential have been suggested to be hallmarks of aging. Here, we investigated whether muscle- and bone-derived MSCs of patients with osteoarthritis and osteoporosis are affected by this exhaustion, compared to healthy donors. Methods: Patients with primary osteoarthritis, femoral neck fractures due to osteoporosis, and healthy donors (controls) were included. MSCs were isolated from the skeletal muscle and subchondral bone from each patient and compared using ex vivo and in vitro analyses, including immunophenotyping, colony-forming unit fibroblast assays, growth kinetics, cell senescence, multilineage potential, and MSC marker gene expression profiling. Results: Freshly isolated cells from muscle from patients with osteoarthritis showed a lower proportion of CD45/CD19/CD14/CD34-negative cells compared to patients with osteoporosis and healthy donors. Freshly isolated muscle cells from patients with osteoarthritis and osteoporosis also showed higher clonogenicity compared to healthy donors. MSCs from both tissues of osteoarthritis patients showed significantly reduced osteogenesis and MSCs from the bone also reduced adipogenesis. Chondrogenic pellet diameter was reduced in bone-derived MSCs from both patient groups compared to healthy donors. A significant positive correlation was observed between adipogenesis and CD271 expression in muscle-derived MSCs. CD73 was significantly lower in bone-derived MSCs from osteoarthritis patients, compared to osteoporosis patients. Gene expression profiling showed significantly lower expression of MSC marker gene leptin receptor, LEPR, previously identified as the major source of the bone and adipocytes in the adult bone marrow, in bone-derived MSCs from patients with osteoarthritis in comparison with osteoporotic patients and healthy donors. Conclusions: Our results show deficient ex vivo and in vitro properties of both skeletal muscle- and bone-derived MSCs in osteoarthritis and osteoporosis patients, compared to healthy donors. In bone-derived MSCs from patients with osteoarthritis, we also identified a lower expression of the leptin receptor, a marker of MSCs that present a major source of MSCs in the adult bone marrow. This suggests that exhaustion of skeletal muscle- and bone-derived MSCs is a hallmark of osteoarthritis and osteoporosis, which defines the need for further clinical trials of stem cell transplantation in these patients.

Tissues of post mortem donors represent valuable alternative sources for the isolation of primary cells with mesenchymal stem/stromal cell (MSC)-like properties. However, the properties of primary cells derived from different tissues and at different post mortem times are poorly recognized. Here, we aim to identify the optimal tissue source between three knee and peri-knee tissues for the isolation of primary cells with MSC-like properties, and to define the influence of the time post mortem on the properties of these cells. We harvested tissues from subchondral bone marrow, synovium and periosteum from 32 donors at various post mortem times. Primary cells were evaluated using detailed in vitro analyses, including colony formation, trilineage differentiation, immunophenotyping and skeletal stem cell marker-gene expression profiling. These data show that the primary cells with MSC-like properties isolated from these three tissues show no differences in their properties, except for higher expression of CD146 in bone-marrow cells. The success rate of the primary cell isolation is dependent on the post mortem time. However, synovium and periosteum cells isolated more than 48 h post mortem show improved osteogenic and chondrogenic potential. This study suggests that knee and peri-knee tissues from donors even 3 days post mortem are strategic sources of MSCs for regenerative procedures.

Human skeletal stem cells (hSSCs) were recently identified as podoplanin (PDPN)/CD73/CD164-positive and CD146-negative cells that decline with age, and play a role in the pathogenesis of osteoarthritis (OA). The aim of this study was to identify the hSSC-like properties of bone-derived mesenchymal stem/stromal cells (MSCs) of patients with late and early OA. Methods: First, we performed gene expression profiling for the hSSC markers in 32 patients with late and early OA, and donors without OA. Having identified the low expression of hSSC markers in late OA patients, we further performed trilineage differentiation and immunophenotyping for hSSC makers in the selected subsets from each donor group. Results: Our results show no differences in osteogenesis, chondrogenesis, and adipogenesis between the MSCs from the three groups. However, the immunophenotyping shows lower CD164 in MSCs from early OA patients in comparison with late and no OA subjects (p = 0.002 and p = 0.017). Conclusions: Our study shows that the in vitro hSSC-like properties of bone-derived MSCs are similar in patients with early and late OA, and in donors without OA. However, the lower percentage of CD164-positive MSCs in early OA patients indicates the potential of CD164 as a marker of the onset of OA.

Background/Objectives: Osteoarthritis (OA) mechanisms are extensively investigated to enable the development of improved diagnostics and therapeutic strategies. Cadaveric tissues are frequently used as “healthy” comparators in mechanistic studies and as laboratory models for the development of new surgical techniques and biomechanical studies. In parallel, advanced cell-based therapies for OA are emerging; however, their usage remains limited, particularly because of the restricted availability and variability of living donor tissues. This review evaluates the contribution of cadaveric tissues to our understanding of OA pathogenesis, diagnosis, and treatment development. Methods: A PRISMA-compliant literature search was conducted in PubMed, Web of Science, and Scopus. Studies involving cadaveric human tissues in OA research were included; animal studies, reviews, and clinical studies without cadaveric samples were excluded. Results: A total of 120 records were identified, of which 52 met the inclusion criteria. Most studies (n = 22) used cadaveric tissues to investigate mechanisms of joint degeneration and OA pathophysiology. The remaining studies were distributed between the development or optimization of diagnostic techniques (n = 9) and orthopedic or related therapeutic approaches (n = 21). Studies exploring cellular therapies derived from cadaveric tissues were scarce and were predominantly identified through citation tracking and reference list screening. Conclusions: Cadaveric studies have contributed to OA research, particularly in the elucidation of its mechanisms. Their potential in the development of cadaveric-derived cellular therapies for regenerative medicine is still in a preliminary phase of development and analysis. Future research should prioritize standardization and optimization of such approaches for eventual clinical applications.

Air embolism is an uncommon but well-recognized cause of sudden death, most frequently encountered in iatrogenic settings. Traumatic air embolism is rare and typically associated with injuries of the head, neck, or thorax. We report an exceptional occupational fatality caused by massive systemic air embolism following penetrating facial trauma. A high-pressure industrial pump component ruptured and was propelled into the worker’s right infraorbital region, producing fractures of the orbital floor and skull base with laceration of the right cavernous and sigmoid venous sinuses. Autopsy revealed extensive intravascular and extravascular gas throughout the body, including the heart, abdominal tissues, and subcutaneous planes. Gas aspirated from the right atrium was analyzed by gas chromatography-mass spectrometry and demonstrated an air-like composition consisting of nitrogen, oxygen, and carbon dioxide. No alternative lethal, traumatic, or natural pathology was identified. This case highlights a rare anatomic portal for the forced entry of air into the venous system. It further demonstrates the value of combined autopsy, radiologic, and chemical analyses in the forensic diagnosis of fatal air embolism.