title: Migration of bone marrow-derived cells for endogenous repair in a new tail-looping disc degeneration model in the mouse: a pilot study.
abstract: BACKGROUND
  Mobilization and homing of bone marrow-derived cells (BMCs) play a pivotal role in healing and regeneration of various tissues. However, the cellular response of BMCs in avascular tissue such as the intervertebral disc (IVD) has not been studied in detail. One of the main obstacles to this is a lack of a suitable mouse disc degeneration model.
  
  
  OBJECTIVE
  The purpose of this study was to establish a reproducible disc degeneration mouse model suitable for analyzing the cellular response of the disc microenvironment and to determine whether BMCs are recruited into the IVD.
  
  
  METHODS
  An experimental animal study of disc degeneration investigating the potential of BMCs in an endogenous repair of the IVD.
  
  
  METHODS
  We transplanted whole bone marrow cells from mice ubiquitously expressing enhanced green fluorescent protein into lethally irradiated mice. Intervertebral disc degeneration was induced through uneven loading by creating a loop in the tail of these mice. The vertebral bone-disc-vertebral bone units were harvested, and BMCs were identified by immunohistochemistry.
  
  
  RESULTS
  A new disc degeneration model was established in the mouse. Applying this model in the bone marrow chimeric mice increased the number of BMCs in the peripheral bone marrow and vascular canals in the endplate, and some were found in the IVD. The migration of BMCs was related to the severity of IVD degeneration.
  
  
  CONCLUSIONS
  Although providing a new disc degeneration model in mice, the present study provides evidence to suggest that although BMCs are recruited during disc degeneration, only a limited number of BMCs migrate to the IVD, presumably because of its avascular nature. This fact provides important elements for developing new treatments as many growth factors and compounds are being tested, both in investigational levels and clinical trials to nourish resident endogenous cells during the degenerative process.
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; AO Spine Research Network. Electronic address: daisakai@is.icc.u-tokai.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakajima
authors.affiliation: AO Spine Research Network; Musculoskeletal Regeneration Program, AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.affiliation: AO Spine Research Network; Musculoskeletal Regeneration Program, AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.affiliation: Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Mochida
mesh_terms: D000818:Animals; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010865:Pilot Projects; D012038:Regeneration / Q000502:physiology*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Bone marrow chimera; Bone marrow–derived cells; Disc degeneration; Intervertebral disc; Mouse model; Spinal deformity; Stem cells