Recombinant Human Keratinocyte Growth Factor Ameliorates Cancer Treatment-Induced oral Mucositis on a Chip.

Oral mucositis (OM) is a severe complication of cancer therapies caused by off-target cytotoxicity. Palifermin, which is recombinant human keratinocyte growth factor (KGF), is currently the only mitigating treatment available to a subset of OM patients. Determining the cell and molecular mechanisms of cancer treatment-induced OM and the anti-mucositis effects of KGF will aid in identifying effective future treatments. This study evaluates a previously developed oral mucositis on a chip (OM-OC) as a screening platform for anti-mucositis treatments, using KGF as a well-studied example. The OM-OC model comprises a confluent keratinocyte layer attached to a basement membrane-lined subepithelial layer consisting of fibroblasts and endothelial cells in a stable collagen gel. Mucositis effects were induced by cisplatin, radiation, and combined treatment followed by a recovery period. Cell damage, barrier dysfunction, and molecular expression during OM induction and resolution were assessed via widefield microscopy, viability and toxicity assays, and antibody arrays. Cell and molecular responses were identified during OM induction and resolution with and without KGF treatment at 1-10 ng/mL, consistent with acute damage followed by repair partially enhanced by KGF, and suggest that KGF treatment in vitro does not return levels of some pro-inflammatory cytokines to baseline. This article is protected by copyright. All rights reserved.