Preclinical efficacy and safety evaluation of a topical mesenchymal stem cell derived conditioned media gel for oral mucositis management.

Chemotherapy / radiation induced oral mucositis (OM) poses significant clinical challenges, often leading to pain, malnutrition, treatment delays, and reduced quality of life. Regenerative medicine has been shown to have beneficial value in wound care. Hence, the current study was aimed at evaluating the safety and therapeutic efficacy of Mesenchymal Stem (Stromal) Cell derived Conditioned Media (MSC-CM) formulations (5%, 10%, and 15%) in preclinical models of 5-fluorouracil (5-FU)–induced OM and radiation wounds. The 28-day oral toxicity studies in rats/mice established that the formulations across treatment groups produced no treatment-related adverse effects. The NOAEL was established at 100% MSC-CM concentration. In the 5-FU based OM model, treatment with MSC-CM formulations demonstrated dose-dependent benefits, including significant reductions in ulcer size/ severity, regeneration of mucosal epithelium, and improvements in hematological, biochemical, hepatic, renal, and immunological parameters compromised by 5-FU. Histopathological evaluation revealed that chemotherapy-induced mucosal hyperplasia and blister formation were markedly reduced following MSC-CM treatment. These findings suggested enhanced tissue repair, possibly mediated through autophagy-associated mechanisms. The 15% formulation was most efficacious, yielding 100% survival, a mean ulcer healing score of 71.9%, and near-complete mucosal recovery, followed by 10% and 5% formulations. In the radiation wound healing model, administration of 10% and 15% MSC-CM formulations was well tolerated, as evidenced by stable body weights, and produced visible reductions in redness, hair loss, wound wetness, and oozing compared to controls. Notably, the 10% formulation promoted accelerated wound closure, with significant wound healing as early as day 4–7. Mechanistically, this could be attributed to induction of secretory IL-20 and IL-17 A/F in mice after wound healing gel (WHG) treatment at site of injury, which led to repair and regeneration of radiation-induced wounds. Collectively, these findings establish MSC-CM based topical formulations as safe and effective therapeutic candidates for mitigating chemotherapy and radiation induced toxicities, enhancing tissue regeneration, thereby supporting its translational potential in oral mucositis.