Browsing by Subject "Collagen fibers"

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    Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I- and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Gonçalves Felix, Renato; Carvalho Bovolato, Ana Livia; Cotrim, Ondina Silvia; Leão, Patricia dos Santos; Batah, Sabrina Setembre; Golim, Márjorie de Assis; Velosa, Ana Paula P.; Teodoro, Walcy; Martins, Vanessa; Ferreira Cruz, Fernanda; Deffune, Elenice; Fabro, Alexandre Todorovic; Capelozzi, Vera Luiza
    The immunogenic collagen V (Col V) and the proinflammatory cytokine interleukin (IL)-17 have been implicated in the pathogenesis of multiple autoimmune diseases. Col V is also up-regulated during adipogenesis and can stimulate adipocyte differentiation in vitro. Conditioned medium (CM) generated from adipose- derived mesenchymal stem cells (MSCs) reduces bleomycin (BLM)-induced lung injury in rats, suggesting a crucial role in situ of immunomodulatory factors secreted by MSCs in these beneficial effects. In the present work, we investigated this hypothesis, analyzing levels of plasma inflammatory mediators and inflammatory and fibrotic mediators in the lung tissue of BLM-injured rats after treatment with MSCs and CM. Pulmonary fibrosis was intratracheally induced by BLM. After 10 days, BLM animals were further randomized into subgroups receiving saline, MSCs, or CM intravenously. On days 14 and 21, the animals were euthanized, and the lungs were examined through protein expression of nitric oxide synthase (NOS), IL-17, transforming growth factor-β (TGF-β), vascular endothelial growth factor, endothelin-1, and the immunogenic Col V through histological quantitative evaluation and plasma levels of fibrinogen, Von Willebrand factor, and platelet-derived growth factor (PDGF). Rats that had been injected with MSCs and CM showed a significant increase in weight and significant improvements at 14 and 21 days after intravenous injection at both time points of analysis of plasma fibrinogen, PDGF, and Von Willebrand factor and NOS-2 expression, supporting an early anti-inflammatory action, thus reducing TGF-β and collagen I fibers. In contrast, intravenous injection of CM was able to significantly increase the deposition of Col V fibers and IL-17 on both day 14 and day 21 as compared with the amount observed in rats from the BLM group and MSC groups. In conclusion, this study reinforces previous observations on the therapeutic properties of MSCs and CM and is the first report to demonstrate the association of its actions with immunomodulatory biomarkers on lung tissue. We concluded that adipose-derived stem cells and adipose- derived stem cells-CM modulate an in situ imbalance between collagen I- and Col V-mediated IL-17 immune response, emerging as a promising therapeutic option for recovering from BLM pulmonary fibrosis
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    Collagen fiber arrangement in the normal bladder lamina propria and their potential impact on the pathological substaging of bladder cancer stage T1
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Gofrit, Ofer N.; Yutkin, Vladimir; Duvdevani, Mordechai; Hidas, Guy; Neuman, Tzahi
    The lamina propria (LP) of the urinary bladder lies between the urothelial mucosa and the muscularis propria. This complex stratum is composed of extracellular matrix, several cell types, and collagen types I and III fibers. LP invasion by urothelial carcinoma (progression from stage Ta to T1) is a determinant of bladder cancer advancement. We attempted to characterize collagen fiber arrangement in the LP. This could enrich our understanding of this important layer and potentially provide clues for sub-staging of the T1 bladder cancer. A total of 24 Masson trichrome-stained images of normal bladder, including 12,530 collagen fibers were quantitatively analyzed using the Dragonfly software. The LP was divided according to fiber orientation into superficial LP (SLP, 15% of the thickness) and the deep LP (DLP, 85% of the thickness). Collagen fiber geometry analysis demonstrated that the SLP fibers are more parallel to the urothelium with an average angle of 26°±23° compared to 40°±26° in the DLP (p=3.4x10-144), more packed (average distance to the closest fiber of 0.61±0.67 compared to 0.66±0.77, p=0.0001), and their aspect ratio is considerably longer (average of 1.93±0.12 compared to 0.20±0.11, p=2.84x10-8). No difference was found in fiber perimeter or Feret diameter. Thus, we conclude that bladder collagen fibers are arranged in two distinct layers: a dense-ordered SLP and a loose disorder DLP. This indicates that the physical barrier to cancer cell invasion probably lies in the SLP, immediately underneath the urothelium. Once this barrier is breached, the looser and disorganized DLP poses no remarkable obstacle. Thus, we believe that histology-based subdivisions of stage T1 are expected to fail in providing clinically meaningful prognostic information.