title: A regenerative approach for bone repair in congenital pseudarthrosis of the tibia associated or not associated with type 1 neurofibromatosis: correlation between laboratory findings and clinical outcome.
abstract: OBJECTIVE
  Congenital pseudarthrosis of the tibia (CPT) is a rare orthopedic disease presenting spontaneous fractures that do not heal. The treatment of CPT is characterized by repeated surgical procedures that often fail, with the inevitable outcome of severe disability and amputation. We tested the hypothesis that CPT may benefit from regenerative strategies based on mesenchymal stromal cells (MSC) combined with platelet-rich fibrin (PRF) as a source of growth factors. The aim of the study was to verify whether laboratory testing to assess the osteogenic properties of MSC and the osteo-inductive activity of PRF correlated with the clinical outcome.
  
  
  METHODS
  Ten patients affected by refractory CPT were treated by using MSC derived from the iliac crest (IC-MSC), PRF and lyophilized bone. In six patients, CPT was associated with type 1 neurofibromatosis (NF1). Biochemical, functional and molecular assays were performed to assess the intrinsic osteogenic potential of IC-MSC (cells cultured with fetal calf serum) and the osteo-inductive properties of PRF (cells cultured with autologous serum).
  
  
  RESULTS
  Bone consolidation was obtained in three patients who had CPT and NF1. In these patients, the IC-MSC exposed to autologous serum were able to form mineral nodules in vitro, while the mineralizing ability was totally abrogated in patients with a poor clinical outcome.
  
  
  CONCLUSIONS
  Cell therapy may be a useful tool for the treatment of refractory CPT because it increases the opportunity to achieve effective bone tissue regeneration. Our data suggest that the presence of pro-osteogenic growth factors is an essential requirement for bone healing.
authors: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopaedic Institute, Bologna, Italy. donatella.granchi@ior.it
authors: Donatella
authors: D
authors: Granchi
authors: Valentina
authors: V
authors: Devescovi
authors: Serena Rubina
authors: SR
authors: Baglio
authors: Marina
authors: M
authors: Magnani
authors: Onofrio
authors: O
authors: Donzelli
authors: Nicola
authors: N
authors: Baldini
mesh_terms: D000293:Adolescent; D000818:Animals; D001861:Bone Regeneration; D002417:Cattle; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007085:Ilium / Q000166:cytology / Q000378:metabolism; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009456:Neurofibromatosis 1 / Q000150:complications / Q000473:pathology; D010012:Osteogenesis; D011542:Pseudarthrosis / Q000150:complications / Q000151:congenital* / Q000473:pathology / Q000628:therapy; D044967:Serum / Q000378:metabolism; D013977:Tibia / Q000002:abnormalities / Q000473:pathology; D014182:Transplantation, Autologous / Q000379:methods; D016896:Treatment Outcome
chemical_list: D005337:Fibrin