Hypothermia enhances heme oxygenase 1-expressing mesenchymal stem cell-induced repair of cerebral hypoxia-ischemia
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Department of Anesthesiology, Baoan Maternity and Child Health Hospital, Jinan University, Shenzhen, China
Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
Submission date: 2019-04-07
Final revision date: 2019-05-02
Acceptance date: 2019-06-01
Online publication date: 2019-07-22
Publication date: 2022-04-17
Arch Med Sci 2022;18(6)
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.

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.