Thawed cryopreserved synovial mesenchymal stem cells show comparable effects to cultured cells in the inhibition of osteoarthritis progression in rats.

Intra-articular injections of mesenchymal stem cells (MSCs) can inhibit the progression of osteoarthritis (OA). Previous reports have used cultured MSCs, but the ability to use thawed cryopreserved MSC stocks would be highly advantageous. Our purpose was to elucidate whether thawed cryopreserved MSCs show comparable inhibitory effects on OA progression in rats to those obtained with cultured MSCs. Cultured rat synovial MSCs or thawed MSCs were compared for in vitro viability and properties. The inhibitory effect of thawed MSCs on OA progression was evaluated by injecting cryopreservation fluid and thawed MSCs in meniscectomized rats. Cartilage degeneration was assessed using gross finding and histological scores. Cultured MSCs were then injected into one knee and thawed MSCs into the contralateral knee of the same individual to compare their effects. Cultured MSCs and MSCs thawed after cryopreservation had comparable in vitro colony formation and chondrogenic potentials. In the rat OA model, the gross finding and histological scores were significantly lower in the thawed MSC group than in the cryopreservation fluid group at 8 weeks. Finally, cartilage degeneration did not differ significantly after injection of cultured and thawed MSCs. In conclusion, thawed MSCs showed comparable inhibitory effects on OA progression to cultured MSCs.

Intra-articular Injection of PDGF-BB Explored in a Novel in Vitro Model Mobilizes Mesenchymal Stem Cells From the Synovium Into Synovial Fluid in Rats.

BACKGROUND: Drugs that can induce mesenchymal stem cell (MSC) mobilization from synovium into synovial fluid will enable regenerative medicine in joints without use of exogenous MSCs. An in vitro synovial MSC migration model had previously been developed for screening but had problems in practical application. We herein developed a novel in vitro model, explored cytokines for synovial MSC mobilization with this model, and verified whether MSCs in synovial fluid increase following intra-articular injection of the cytokine. METHODS: Human synovial MSCs embedded in a mixture of Matrigel and type 1 collagen hydrogel were placed on a culture insert and then put in medium containing migration factor. Of the six cytokines, we identified the one that mobilizes the highest number of MSCs. PDGF-BB or PBS was injected into rat knees, and 48 h later, synovial fluid was collected and cultured. The cells were examined for MSC properties. RESULTS: PDGF-BB was the most effective for synovial MSC mobilization among six cytokines. The effect of PDGF-BB was inhibited by a PRGFR inhibitor. Injection of PDGF-BB into rat knees increased colony-forming cells in the synovial fluid. These cells had surface epitopes and multipotency comparable to MSCs and a higher capacity for proliferation, colony formation, and chondrogenesis. CONCLUSIONS: This novel in vitro model recapitulated the migration of MSCs from synovium into synovial fluid. Our exploration of cytokines revealed that PDGF-BB strongly induced in vitro synovial MSC migration, while intra-articular injection of PDGF-BB increased in vivo MSC numbers in synovial fluid in rats.

Hemorrhagic Sudden Onset of Spinal Epidural Angiolipoma.

Angiolipomas are relatively rare benign tumors. Spinal angiolipomas that generally induce slow progressive cord compression are most commonly found in the thoracic region. A 49-year-old female with obesity presented with a 1-week history of progressively worsening back pain, paresthesia of lower limbs, and gait disturbance. When thoracic magnetic resonance imaging (MRI) revealed a dorsal epidural mass at the Th5-Th8 level, the patient underwent a laminectomy for gross total excision of the lesion. Both mature fatty tissue and abnormal proliferating vascular elements with thin or expanded walls were observed in the resected tumor. Nonfiltrating spinal angiolipoma was diagnosed and confirmed by pathology. After the operation, sensory loss, numbness, and gait disturbance were improved following the disappearing severe back pain. Following examinations indicated the absence of recurrence within 1 year. The angiolipomas of the spine are rare causes of spinal cord compression that generally induce slow progressive cord compression, but sudden onset or rapid worsening of neurological deterioration is observed in hemorrhagic spinal angiolipoma.