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A Flowable Placental Formulation Prevents Bleomycin-Induced Dermal Fibrosis in Aged Mice

Smith & Nephew Plc., Columbia, MD 21046, USA
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4242; https://doi.org/10.3390/ijms21124242
Received: 29 April 2020 / Revised: 4 June 2020 / Accepted: 11 June 2020 / Published: 14 June 2020
(This article belongs to the Section Molecular Biology)
Fibrosis, the thickening and scarring of injured connective tissue, leads to a loss of organ function. Multiple cell types, including T-cells, macrophages, fibrocytes, and fibroblasts/myofibroblasts contribute to scar formation via secretion of inflammatory factors. This event results in an increase in oxidative stress and deposition of excessive extracellular matrix (ECM), characteristic of fibrosis. Further, aging is known to predispose connective tissue to fibrosis due to reduced tissue regeneration. In this study, we investigated the anti-fibrotic activity of a flowable placental formulation (FPF) using a bleomycin-induced dermal fibrosis model in aged mice. FPF consisted of placental amnion/chorion- and umbilical tissue-derived ECM and cells. The mice were injected with either FPF or PBS, followed by multiple doses of bleomycin. Histological assessment of FPF-treated skin samples revealed reduced dermal fibrosis, inflammation, and TGF-β signaling compared to the control group. Quantitative RT-PCR and Next Generation Sequencing analysis of miRNAs further confirmed anti-fibrotic changes in the FPF-treated group at both the gene and transcriptional levels. The observed modulation in miRNAs was associated with inflammation, TGF-β signaling, fibroblast proliferation, epithelial-mesenchymal transition and ECM deposition. These results demonstrate the potential of FPF in preventing fibrosis and may be of therapeutic benefit for those at higher risk of fibrosis due to wounds, aging, exposure to radiation and genetic predisposition. View Full-Text
Keywords: amnion; chorion; umbilical tissue; inflammation; oxidative stress amnion; chorion; umbilical tissue; inflammation; oxidative stress
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MDPI and ACS Style

Dhall, S.; Lerch, A.; Johnson, N.; Jacob, V.; Jones, B.; Park, M.S.; Sathyamoorthy, M. A Flowable Placental Formulation Prevents Bleomycin-Induced Dermal Fibrosis in Aged Mice. Int. J. Mol. Sci. 2020, 21, 4242. https://doi.org/10.3390/ijms21124242

AMA Style

Dhall S, Lerch A, Johnson N, Jacob V, Jones B, Park MS, Sathyamoorthy M. A Flowable Placental Formulation Prevents Bleomycin-Induced Dermal Fibrosis in Aged Mice. International Journal of Molecular Sciences. 2020; 21(12):4242. https://doi.org/10.3390/ijms21124242

Chicago/Turabian Style

Dhall, Sandeep, Anne Lerch, Nicholas Johnson, Vimal Jacob, Brielle Jones, Min S. Park, and Malathi Sathyamoorthy. 2020. "A Flowable Placental Formulation Prevents Bleomycin-Induced Dermal Fibrosis in Aged Mice" International Journal of Molecular Sciences 21, no. 12: 4242. https://doi.org/10.3390/ijms21124242

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