Injectable Cellular Placental Formulation Prevents Bleomycin Induced Dermal Fibrosis In Aged Mice
Sandeep Dhall, Vimal Jacob, Reda Proctor, Brielle Johnson, Nicholas Johnson, Anne Lerch, Jin-Qiang Kuang, Malathi Sathyamoorthy, Alla Danilkovitch.
Osiris Therapeutics Inc., Columbia, MD, USA.
BACKGROUND Fibrosis, the thickening and scarring of an injured connective tissue due to excessive extracellular matrix (ECM) deposition, leads to loss of organ function. Multiple cells types including platelets, neutrophils, mast cells and macrophages, fibrocytes, fibroblasts and myofibroblasts contribute to scar formation via secretion of inflammatory factors that lead to an increase in oxidative stress and abnormal ECM deposition. Aging is a known factor associated with reduction in tissue regeneration and predisposition to fibrosis.
METHODS In this study we investigated the anti-fibrotic activity of an injectable cellular placental formulation (ICPF) using a bleomycin-induced dermal fibrosis model in 22 months old C57Bl/6 mice. The ICPF consisted of a mixture of placental amnion/chorion and umbilical cord tissue derived extracellular matrix and cells. Two groups of mice (n=6) received either 100μL of ICPF (treatment) or PBS (control) injection in the middle of a 1x1 cm2 area drawn on the upper dorsa of each mouse. Then, a total of 10 doses of bleomycin (100μl of 0.5mg/mL each time) were subcutaneously administered every other day for 21days at 5 points within the 1x1 cm2 area: the first four injections were administered into four different corners of the square followed by the fifth injection given in the middle of the square. After the completion of bleomycin injections skin samples were collected for histological analysis and RNA tissue extraction for PCR.
RESULTS Histological analysis showed no dermal fibrosis in the ICPF-treated animals, however epidermal hyperplasia and myofiber degeneration were evident in the control group. PCR array for 84 genes involved in regulation of inflammation and wound healing confirmed pathological changes in the control group.
CONCLUSIONS Results of this study demonstrate ICPF’s potential to prevent fibrosis, which may have a therapeutic value for patients at higher risk for fibrosis due to aging, genetic predisposition, or exposure to radiation.
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