title: Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.
abstract: Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America ; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors: Li-Li
authors: LL
authors: Wang
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Dongdong
authors: D
authors: Chen
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Jinhwan
authors: J
authors: Lee
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Xiaohuan
authors: X
authors: Gu
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Ghina
authors: G
authors: Alaaeddine
authors: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors: Jimei
authors: J
authors: Li
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America ; Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Ling
authors: L
authors: Wei
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Shan Ping
authors: SP
authors: Yu
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D010281:Parathyroid Hormone; D040301:Vascular Endothelial Growth Factor Receptor-2