title: Promotion of bone repair by implantation of cryopreserved bone marrow-derived mononuclear cells in a rabbit model of steroid-associated osteonecrosis.
abstract: OBJECTIVE
  Cytotherapy is an insufficient method for promoting bone repair in steroid-associated osteonecrosis (SAON), and this has been attributed to impairment of the bioactivity of bone marrow-derived stem cells (BMSCs) after pulsed administration of steroids. Cryopreserved autologous bone marrow-derived mononuclear cells (BMMNCs), which contain BMSCs, might maintain their bioactivity in vitro. This study sought to investigate the effects of cryopreserved BMMNCs, before steroid administration, on the enhancement of bone repair in an established rabbit model of SAON.
  
  
  METHODS
  For in vitro study, bone marrow was harvested 4 weeks before SAON induction from the iliac crests of rabbits (n = 10) to isolate fresh BMMNCs, and the BMMNCs were then cryopreserved for 8 weeks. Both the fresh and the cryopreserved BMMNCs were evaluated for their bioactivity and osteogenic differentiation capacity. In addition, BMMNCs were isolated 2 weeks after SAON induction and subjected to the same evaluations. For in vivo study, cryopreserved BMMNCs were implanted into the bone tunnel during core decompression of the femur (n = 12 rabbits) after the induction of SAON, and tissue regeneration was evaluated by micro-computed tomography and histologic analyses at 12 weeks postoperation.
  
  
  RESULTS
  In vitro, there were no significant differences in the bioactivity or ability to undergo osteogenic differentiation between fresh BMMNCs and cryopreserved BMMNCs, but after SAON induction, both features were decreased significantly. In vivo, the bone mineral density, ratio of bone volume to total volume of bone, and volume and diameter of neovascularization within the bone tunnel were significantly higher in the BMMNC-treated group compared to the nontreated control group at 12 weeks postoperation.
  
  
  CONCLUSIONS
  Cryopreserved BMMNCs maintained their bioactivity and promoted bone regeneration and neovascularization within the bone tunnel after core decompression in this rabbit model of SAON.
authors.affiliation: The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Xie
authors.forename: Xin-Luan
authors.initials: XL
authors.lastname: Wang
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: He
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Sheng
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D001861:Bone Regeneration / Q000502:physiology*; D015925:Cryopreservation; D004195:Disease Models, Animal; D005270:Femur Head / Q000187:drug effects / Q000473:pathology; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D005938:Glucocorticoids / Q000633:toxicity; D008297:Male; D008775:Methylprednisolone / Q000633:toxicity; D009000:Monocytes / Q000637:transplantation*; D010020:Osteonecrosis / Q000628:therapy*; D011817:Rabbits
chemical_list: D005938:Glucocorticoids; D008775:Methylprednisolone