Restoration of tissue damage, and never activity after hypoxia-ischemia by implantation of peripheral blood mononuclear cells.
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 24h 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.
['Liu|Yu-xiao|YX|', 'Guo|Xiao-ming|XM|', 'Li|Jun-feng|JF|', 'Meng|Yu|Y|', 'Zhang|Hai-tao|HT|', 'Liu|Ai-jun|AJ|', 'Li|Shou-chun|SC|', 'Liu|Yuan-lin|YL|', 'Zhu|Heng|H|', 'Xue|Jing-hui|JH|', 'Zhang|Yi|Y|', 'Zhang|Zhi-wen|ZW|']
D000818:Animals D017209:Apoptosis D001921:Brain D002465:Cell Movement D002470:Cell Survival D054377:Chemokine CXCL12 D016179:Granulocyte Colony-Stimulating Factor D019650:Hematopoietic Stem Cell Mobilization D006801:Humans D020925:Hypoxia-Ischemia, Brain D007963:Leukocytes, Mononuclear D009043:Motor Activity D051381:Rats D017207:Rats, Sprague-Dawley
Peripheral blood mononuclear cells Peripheral blood mononuclear cells HI PB-MNCs Cell transplantation Migration Stromal cell-derived factor-1 Stromal cell-derived factor-1 SDF-1 ANOVA BM-MNCs CB-MNCs CsA G-CSF GFAP HE Hypoxia–ischemia encephalopathy SD Sprague-Dawley TTC analysis of variance bone marrow mononuclear cord blood mononuclear cyclosporine A glial fibrillary acidic protein granulocyte colony-stimulating factor hematoxylin and eosin hypoxia–ischemia peripheral blood mononuclear cells stromal cell-derived factor-1 triphenyltetrazolium chloride