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Lab Research
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Product characterization and preclinical wound healing studies with living allogeneic dermal fbroblasts on biodegradable microcarriers in a gel* First Author: Jiejing Xu Authors: J. Xu, N.S. Bashir, C. Peng, P. Lagosky, T. Ganendran, J. Connelly Physiologic mechanisms potentially contributing to the activity of cell-based treatments for chronic and cell-depleted wounds are relatively poorly defined. Characterization of the properties of a new topical product containing viable allogeneic human dermal fibroblasts on biodegradable microcarriers formulated in a gel matrix* was approached via in vitro assays and studies in animal models. Cell culture supernatants used in product manufacture and the cell-free storage matrix collected from the final product were assayed for a range of cytokines and growth factors using custom-made protein arrays. Time-dependent profiles showed that all samples contained significant amounts of VEGF, IL-8, IL-6, FGF-basic, KGF, TGF-ß1, PDGF-BB, IGF-II and collagen IV, and TGF-a, TGF-ß3, IGF-I and GM-CSF at low levels. IL-1ß and PDGF-AA were not detected, and IL-1a was found only in cell culture supernatant. Levels of VEGF and IL-8 increased on storage. Full-thickness, acute wounds in pigs treated with the product showed evidence of enhanced dermal revascularisation and collagen regeneration. Human fibroblasts delivered to wounds in athymic mice produced collagen I, laminin, fibronectin, and VEGF. The biodegradable microcarriers produced a transient inflammatory response that may also promote healing. The in vitro and in vivo findings were combined to suggest a mode of product action. *Product notation: Regenadermª, ApoPharma, Inc. Toronto, ON |
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