Adipose-derived Stem Cells Alleviate Acute Pancreatitis by Inhibiting Ferroptosis and Oxidative Damage in Canine

Background Canine acute pancreatitis (AP) is a common exocrine pancreatitis disease that can lead to systemic inflammatory response syndrome and multi-organ failure. This study aims to investigated the potential therapeutic benefits of adipose-derived stem cells (ADSCs) and conditioned medium (CM) in managing canine AP and the role in ferroptosis regulation. Methods Sixteen dogs were randomly divided into control (CON), AP, ADSCs and CM group. The AP model were established by injecting sodium taurocholate (5%, 0.1 mL/kg) and trypsin (3500 U/kg) through the pancreaticobiliary duct. ADSCs (1×10 ⁶ /kg) and CM (0.1 mL/kg) were injected intravenously at 6 h after surgery, and the roles on ferroptosis and oxidative stress were analyzed. In addition, the changing pattern of ferroptosis and oxidative stress were investigated by LPS-induced cellular inflammation model of AR42J in vitro. Results Our study showed that ferroptosis occurs in the pancreas during AP, as evidenced by significant iron accumulation, with suppressed glutathione peroxidase 4 (GPx4) expression and increased transferrin receptor-1 (TFR1) and ferritin heavy chain (FTH). ADSCs and ADSCs-CM treatment achieved pathological remission and effectively restored abnormal amylase (AMY), lipase (LIPA) levels. ADSCs-CM showed similar ferroptosis alleviating effects as ADSCs treatment, with reduced iron accumulation and increased GPx4 expression. Furthermore, ADSCs promote nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus and initiate transcription of detoxification enzymes to protect the pancreas from oxidative damage. Conclusions Based on these findings, ADSCs protect the pancreas by inhibiting ferroptosis and oxidative stress via paracrine function, which could be a therapeutic target for AP.