title: Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice.
abstract: Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord 1 week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury.
authors.affiliation: Department of Orthopaedic Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan. kossy-z@gb3.so-net.ne.jp
authors.forename: Shuhei
authors.initials: S
authors.lastname: Koshizuka
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Murasawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Takahito
authors.initials: T
authors.lastname: Kamada
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Masazumi
authors.initials: M
authors.lastname: Murakami
authors.forename: Hideshige
authors.initials: H
authors.lastname: Moriya
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000628:therapy*