Restoration of tissue damage, and never activity after hypoxia–ischemia by implantation of peripheral blood mononuclear cells

•We reported a simple and effective therapeutic approach for HI encephalopathy.•Peripheral blood mononuclear cells survived and located in the damage area of brain.•Peripheral blood mononuclear cells expressed neural marker after transplantation.•Cell therapy reduced motor impairment, lesion volume and nerve cell apoptosis of rats.•Migration of cells might be dictated by the damaged brain via SDF-1-dependent pathway.

Hypoxia–ischemia (HI) encephalopathy is a frequent cause of disability and mortality with limited therapeutic options. Here, we collected peripheral blood mononuclear cells (PB-MNCs) from healthy donors and labeled them with CM-DiI before implanting these cells by tail-vein injection into rats at day 3 after hypoxia–ischemia (HI). For immune-suppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 h before cell transplantation. Then we observed the PB-MNCs by fluorescent microscopy, examined motor function of rats by rotarod and cylinder tests, measured the lesion volume using image-pro plus software, and analyzed the apoptosis of neural cells in HI rats by tunnel assay. The results showed PB-MNCs could survive in the brain of hosts, migrate to the damage area and express neural marker. In addition, The HI rats that received PB-MNCs showed a reduction in motor function impairment, lesion volume and neural cell apoptosis. To better understand the mechanism of cell migration, PB-MNCs were also injected into normal rats via tail-vein. The expression of stromal cell-derived factor-1 (SDF-1) in the brain of normal and HI rats was measured by RT- PCR and western-blot, while the response of PB-MNCs in vitro to HI or normal brain extracts were measured by cell migration assay. Collectively these data suggest that the migration of PB-MNCs is directed to the damaged brain through an SDF-1-dependent pathway. Our results suggest that intravenous transplantation of PB-MNCs may be a feasible candidate for HI therapy.