Tissue fibrosis is associated with the aging process of most of our organs, and organ aging correlates with the chronic accumulation of senescent cells. Fibrosis occurs when fibroblasts proliferate and deposit pathological amounts of extracellular matrix (ECM), leading to progressive tissue scarring and organ dysfunction. Fibroblasts play a key role in fibrosis, especially in the skin where fibroblasts are the most abundant cell type in the dermis and are mainly responsible for the synthesis of ECM. This study aims to investigate how senescent fibroblasts and their secretome influence dermal fibrosis. Here we used human dermal fibroblasts (HDFs) treated with doxorubicin (doxo) to induce senescence. The senescent phenotype of these stress-induced premature senescent (SIPS) cells was confirmed with several markers. The expression of pro-fibrotic genes was quantified and finally, the impact of their secretome on the fibrotic response of non-senescent fibroblasts was assessed. Doxorubicin treatment, induced senescence in fibroblasts which has been confirmed with elevated senescence-associated β- galactosidase (SA-β-gal) activity, absence of BrdU incorporation, upregulation of p21, and loss of Lamin b1. Expression levels of the pro-fibrotic genes ACTA2 and FN1 increased in SIPS cells, but in contrast to studies using lung fibroblasts the secretome of these cells failed to induce a paracrine fibrotic response in non-senescent cells. In general, these results suggest that these senescent cells are potentially profibrotic, and their accumulation can trigger fibrosis in organs.
Background & Objective: Nowadays, the use of natural materials in regenerative medicine is very important, especially using substances with calcium carbonate structure due to their similarity to the bone structure. In this study, the effect of Cerastoderma lamarcki shell and rice bran extract on stem cell proliferation and differentiation has been investigated. Materials & Methods: First, crastoderma shells were collected and cut into small pieces. Its compounds were analyzed by X-ray diffraction. Finally, the structural features of shells were investigated by SEM. Stem cells were extracted and cultured from the umbilical cord of Wharton's jelly. After cells seeding on the scaffold, cell survival was studied by MTT. Adhesion, morphology, and diffusion of cells on the shells were also examined by SEM. Cells were stimulated by osteogenic medium and osteoblastic differentiation by alkaline phosphatase activity was studied. Rice bran ethanolic extract was used. Cell survival was studied by MTT technique and osteogenic differentiation was studied by Alizarin Red staining. Results: MTT studies showed appropriate adhesion of cells on the scaffold and SEM studies also showed successful binding and their appropriate morphology on the scaffold. Alkaline phosphatase studies showed that osteogenic differentiation of cells on shells is significant. In another part of this study, we studied the survival and osteogenic differentiation of these cells in treatment with ethanolic extract of rice bran. MTT studies showed a dose-dependent decrease in cell survival in the presence of the extract. Alizarin staining also showed the differentiation potential of this substance. Conclusion: The results showed the appropriate potential of these two natural substances in bone differentiation. However, further studies are needed to prove their effects.
Tissue fibrosis is associated with the aging process of most of our organs, and organ aging correlates with the chronic accumulation of senescent cells. Fibrosis occurs when fibroblasts proliferate and deposit pathological amounts of extracellular matrix (ECM), leading to progressive tissue scarring and organ dysfunction. Fibroblasts play a key role in fibrosis, especially in the skin where fibroblasts are the most abundant cell type in the dermis and are mainly responsible for the synthesis of ECM. This study aims to investigate how senescent fibroblasts and their secretome influence dermal fibrosis. Here we used human dermal fibroblasts (HDFs) treated with doxorubicin (doxo) to induce senescence. The senescent phenotype of these stress-induced premature senescent (SIPS) cells was confirmed with several markers. The expression of pro-fibrotic genes was quantified and finally, the impact of their secretome on the fibrotic response of non-senescent fibroblasts was assessed. Doxorubicin treatment, induced senescence in fibroblasts which has been confirmed with elevated senescence-associated β- galactosidase (SA-β-gal) activity, absence of BrdU incorporation, upregulation of p21, and loss of Lamin b1. Expression levels of the pro-fibrotic genes ACTA2 and FN1 increased in SIPS cells, but in contrast to studies using lung fibroblasts the secretome of these cells failed to induce a paracrine fibrotic response in non-senescent cells. In general, these results suggest that these senescent cells are potentially profibrotic, and their accumulation can trigger fibrosis in organs.
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