LAUSR

Mesenchymal stem cells (MSC) are known to exhibit potency for the repair of cerebral hypoxia-ischemia (HI). Heme oxygenase 1 (HO-1) is capable of inducing repair and can boost stem cell-based therapeutic effects. Hypothermia is known to have strong cytoprotective effects.HO-1 secreting lentiviral vector was constructed and transfected into MSC. HO-1 secretion from HO-1/MSC was verified using Western blot, real-time PCR and ELISA tests. The proliferation and anti-oxidative abilities of HO-1/MSC were detected by CCK-8 assay and biochemical kits. The therapeutic efficacy of HO-1/MSC in a rat cerebral HI model under normothermia or hypothermia was then tested. The cells were transplanted into HI animal models and the rats were kept at 37°C or 25°C. The histological pathology, apoptosis and behavior were analyzed with Nissl stain, TUNEL analysis, and rotarod and cylinder tests respectively. MSC survival and differentiation in vivo were also analyzed by immunofluorescence.HO-1 secretions promoted the proliferation and anti-oxidative abilities of MSC. The HO-1/MSC significantly improved the apoptosis, injury, behavior and enhanced MSC survival and differentiation into mature neurons and oligodendrocytes. Moreover, HO-1/MSC significantly enhanced repair of HI under hypothermia.These results suggest that HO-1-secreting MSC under hypothermia is an effective therapeutic approach for the treatment of HI.