title: Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment.
abstract: BACKGROUND
  Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution.
  
  
  OBJECTIVE
  We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation.
  
  
  RESULTS
  Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation.
  
  
  CONCLUSIONS
  Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.
authors.affiliation: Dept. of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Giannotti
authors.forename: Luisa
authors.initials: L
authors.lastname: Trombi
authors.forename: Vanna
authors.initials: V
authors.lastname: Bottai
authors.forename: Marco
authors.initials: M
authors.lastname: Ghilardi
authors.forename: Delfo
authors.initials: D
authors.lastname: D'Alessandro
authors.forename: Serena
authors.initials: S
authors.lastname: Danti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Dell'Osso
authors.forename: Giulio
authors.initials: G
authors.lastname: Guido
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057176:Compassionate Use Trials; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D019736:Prostheses and Implants; D011542:Pseudarthrosis / Q000628:therapy*; D033581:Stem Cell Transplantation; D013997:Time Factors; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D005337:Fibrin
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