Effects of mesenchymal stem cells on post-resuscitation renal and intestinal injuries in a porcine cardiac arrest model.

OBJECTIVES: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes post-resuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries following cardiopulmonary resuscitation (CPR) in a porcine CA model.

METHODS: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. MSCs were differentiated from human embryonic stem cells, and then intravenously administered at a dose of 2.5 × 106/kg at 1.5 and 3 d prior to the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid-binding protein (IFABP), and diamine oxidase (DAO) at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues.

RESULTS: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of Cr, BUN, IFABP, and DAO were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSCs administration significantly decreased the levels of renal and intestinal injury biomarkers compared to those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group.

CONCLUSIONS: MSCs administration was effective in alleviating post-resuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.