The mammalian tissue extracellular matrix (ECM) has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. However, the material properties of decellularized ECM (dECM) from in vitro cell cultures and the effect of these properties on wound remodeling remain unclear. To elucidate its biological activity, we extracted dECM from human lung fibroblasts, fabricated it into a patch, and applied it to a full-thickness skin wound. The fibroblast-derived dECM (fdECM) maintained the content of collagen Ⅰ, collagen Ⅳ, and elastin, and the extraction process did not damage its critical growth factors. The fdECM-conjugated collagen patch (COL-fdECM) facilitated wound contraction and angiogenesis in the proliferative phase when applied to the in vivo full-thickness skin wound model. Moreover, the COL-fdECM treated wound showed increased regeneration of the epidermal barrier function, mature collagen, hair follicle, and subepidermal nerve plexus, suggesting qualitative skin remodeling. This therapeutic efficacy was similarly observed when applied to the diabetic ulcer model. fdECM was shown to help remodel the tissue by regulating fibroblast growth factors, matrix metalloproteinases, and tissue inhibitors of metalloproteinases via the p38 and ERK signaling pathways in an in vitro experiment for understanding the underlying mechanism. These results provide a biological basis for cell-derived ECM as a multi-functional biomaterial applicable to various diseases.
A 6-year-old female Maltese dog presented with a cervical mass without pain. The tumor was surrounded by a thick fibrous tissue and consisted of an osteoid matrix with osteoblasts and two distinct areas: a mesenchymal cell-rich lesion with numerous multinucleated giant cells and a chondroid matrix-rich lesion. The tumor cells exhibited heterogeneous protein expression, including a positive expression of vimentin, cytokeratin, RANKL, CRLR, SOX9, and collagen 2, and was diagnosed as extraskeletal osteosarcoma. Despite its malignancy, the dog showed no sign of recurrence or metastasis three months after the resection. Further analysis of the tumor cells revealed a high expression of proliferation- and metastasis-related biomarkers in the absence of angiogenesis-related biomarkers, suggesting that the lack of angiogenesis and the elevated tumor-associated fibrosis resulted in a hypoxic tumor microenvironment and prevented metastasis.
BackgroundThere is widespread prejudice in veterinary medicine that gout does not occur in non-human mammalians. However, we recently discovered monosodium urate crystals in the synovial fluid obtained from a few dogs and a cat. Since it is the definitive and gold standard to diagnose gout, we report these cases as newly emerging diseases in companion animals.Case PresentationFour dogs and one cat were presented at our hospital because of lameness due to an unknown cause. Even after the routine examinations, including radiographic imaging, laboratory examination, and arthrocentesis, we were unable to find a clear cause of polyarthritis. However, we later discovered monosodium urate crystals in the synovial fluid of the animals, confirmed by polarized microscopy. In one of the two dogs treated with immunosuppressants, the disease relapsed, and the other did not show any symptoms for 3 months. The other two dogs were treated with xanthine oxidase inhibitor, where one died, and the other did not show any symptoms for 3 years. The cat was treated with drainage and intra-articular dexamethasone injection, but the disease recurred after 6 months.ConclusionThis is the first report to confirm that articular gout can occur in dogs and cats. Care must be taken not to neglect needle-shaped materials in the synovial fluid. Gout should also be included in the differential diagnosis of arthritis and further research is needed in these animals.
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