Open AccessHypothermia enhances heme oxygenase 1-expressing mesenchymal stem cell-induced repair of cerebral hypoxia-ischemia
Author(s) -
Xuetao Yan,
Xiaoli Cheng,
XiangHu He,
Wenzhong Zheng,
Xiaoyi Yuan,
Chen Hu
Publication year - 2019
Publication title -
archives of medical science/archives of medical science (online)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 46
eISSN - 1896-9151
pISSN - 1734-1922
DOI - 10.5114/aoms.2019.86784
Subject(s) - mesenchymal stem cell , heme oxygenase , medicine , apoptosis , hypoxia (environmental) , hypothermia , tunel assay , pharmacology , ischemia , immunology , pathology , heme , biology , immunohistochemistry , biochemistry , oxygen , chemistry , organic chemistry , enzyme
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. Material and methods 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. Results 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. Conclusions These results suggest that HO-1-secreting MSC under hypothermia is an effective therapeutic approach for the treatment of HI.