title: New preclinical porcine model of femoral head osteonecrosis to test mesenchymal stromal cell efficiency in regenerative medicine.
abstract: OBJECTIVE
  In order to evaluate new therapeutic approaches to human osteonecrosis of the femoral head (ONFH), this study proposed to improve the existing animal model by developing a new surgically induced pig model.
  
  
  METHODS
  First, ONFH was induced with an easy and minimally invasive technique: cryogenic insult with repeated freeze-thaw cycle. Then, to compare and improve the efficacy of this first method, we combined the cryogenic insult to vascular coagulation of the posterior circumflex vessels.
  
  
  RESULTS
  Cryoinjury with repeated freeze-thaw cycle alone is sufficient to induce, three weeks postsurgery, a subchondral necrosis as confirmed by magnetic resonance imaging (MRI) and histological analysis. However, a bone regeneration began at four weeks and was complete at eight weeks. To optimise this result, we combined cryoinjury with posterior circumflex vessel coagulation and observed the persistence of ONFH, with progression to collapse at 14 weeks postinduction.
  
  
  CONCLUSIONS
  Cryoinjury associated with partial vascular coagulation is sufficient to obtain localised and sustainable necrosis in the subchondral area of the femoral head, reproducing all stages of the human disorder. The co-analysis by MRI and histology allowed us to confirm that the classic T1- and T2-weighted hyposignal regeneration front around a fatty high T1-weighted signal observed by MRI indicate signs of induced osteonecrosis. Our results indicate that our pig model induces all stages of human ONFH, which can be followed by MRI, making it relevant for clinical trials.
authors.affiliation: Faculté de Médecine, Laboratoire de "Bioingénierie Cellulaire, Tissulaire et Sanguine", Université Paris-Est, EA3952, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Poignard
authors.forename: Angélique
authors.initials: A
authors.lastname: Lebouvier
authors.forename: Madeleine
authors.initials: M
authors.lastname: Cavet
authors.forename: Alain
authors.initials: A
authors.lastname: Rahmouni
authors.forename: Charles-Henri
authors.initials: CH
authors.lastname: Flouzat Lachaniette
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.forename: Hélène
authors.initials: H
authors.lastname: Rouard
authors.forename: Philippe
authors.initials: P
authors.lastname: Hernigou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chevallier
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods* / Q000451:nursing*; D003080:Cold Temperature / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D005271:Femur Head Necrosis / Q000209:etiology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D059630:Mesenchymal Stem Cells; D044968:Regenerative Medicine / Q000379:methods*; D013552:Swine; D016896:Treatment Outcome