title: Safety and feasibility of cell-based therapy of autologous bone marrow-derived mononuclear cells in plate-stabilized proximal humeral fractures in humans.
abstract: Local implantation of ex vivo concentrated, washed and filtrated human bone marrow-derived mononuclear cells (BMC) seeded onto β-tricalciumphosphate (TCP) significantly enhanced bone healing in a preclinical segmental defect model. Based on these results, we evaluated in a first clinical phase-I trial safety and feasibility of augmentation with preoperatively isolated autologous BMC seeded onto β-TCP in combination with angle stable plate fixation for the therapy of proximal humeral fractures as a potential alternative to autologous bone graft from the iliac crest.
  
  
  
  10 patients were enrolled to assess whether cell therapy with 1.3 × 106autologous BMC/ml/ml β-TCP, collected on the day preceding the definitive surgery, is safe and feasible when seeded onto β-TCP in patients with a proximal humeral fracture. 5 follow-up visits for clinical and radiological controls up to 12 weeks were performed.
  
  
  
  β-tricalciumphosphate fortification with BMC was feasible and safe; specifically, neither morbidity at the harvest site nor at the surgical wound site were observed. Neither local nor systemic inflammation was noted. All fractures healed within the observation time without secondary dislocation. Three adverse events were reported: one case each of abdominal wall shingles, tendon loosening and initial screw perforation, none of which presumed related to the IND.
  
  
  
  Cell therapy with autologous BMC for bone regeneration appeared to be safe and feasible with no drug-related adverse reactions being described to date. The impression of efficacy was given, although the study was not powered nor controlled to detect such. A clinical trial phase-II will be forthcoming in order to formally test the clinical benefit of BMC-laden β-TCP for PHF patients. Trial registration The study was registered in the European Clinical Trial Register as EudraCT No. 2012-004037-17. Date of registration 30th of August 2012. Informed consent was signed from all patients enrolled.
authors.affiliation: Department of Trauma Surgery, Johann-Wolfgang-Goethe University, Theodor-Stern-Kai 7, Main, 60590, Frankfurt, Germany. ccseebach@googlemail.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seebach
authors.affiliation: Department of Trauma Surgery, Johann-Wolfgang-Goethe University, Theodor-Stern-Kai 7, Main, 60590, Frankfurt, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Henrich
authors.affiliation: Department of Trauma Surgery, Johann-Wolfgang-Goethe University, Theodor-Stern-Kai 7, Main, 60590, Frankfurt, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Meier
authors.affiliation: Department of Trauma Surgery, Johann-Wolfgang-Goethe University, Theodor-Stern-Kai 7, Main, 60590, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nau
authors.affiliation: Institute for Transfusion Medicine and Immune Hematology, Johann-Wolfgang-Goethe University, and DRK-Blutspendedienst Baden-Württemberg-Hessen, Main, Frankfurt, Germany.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.affiliation: Department of Trauma Surgery, Johann-Wolfgang-Goethe University, Theodor-Stern-Kai 7, Main, 60590, Frankfurt, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Marzi
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology*; D001860:Bone Plates; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D015507:Drugs, Investigational / Q000627:therapeutic use; D023381:Endpoint Determination; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D012784:Shoulder Fractures / Q000097:blood / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy*; D013234:Stem Cells / Q000166:cytology; D014182:Transplantation, Autologous / Q000009:adverse effects
chemical_list: D015507:Drugs, Investigational
keywords: BMC; Bone defect; Bone regeneration; Cell therapy; Proximal humeral fracture