title: Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration.
abstract: BACKGROUND
  Recent approaches have sought to harness the potential of stem cells to regenerate bone that is lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of osteoprogenitors for such applications. However, previous studies indicated that the concentration of osteoprogenitors present in BMA is less than required for robust bone regeneration. We provide further evidence for the importance of BMA enrichment for skeletal tissue engineering strategies using a novel acoustic wave-facilitated filtration strategy to concentrate BMA for osteoprogenitors, clinically applicable for intraoperative orthopedic use.
  
  
  METHODS
  Femoral BMA from 15 patients of an elderly cohort was concentrated for the nucleated cell fraction against erythrocytes and excess plasma volume via size exclusion filtration facilitated by acoustic agitation. The effect of aspirate concentration was assessed by assays for colony formation, flow cytometry, multilineage differentiation and scaffold seeding efficiency.
  
  
  RESULTS
  BMA was filtered to achieve a mean 4.2-fold reduction in volume with a corresponding enrichment of viable and functional osteoprogenitors, indicated by flow cytometry and assays for colony formation. Enhanced osteogenic and chondrogenic differentiation was observed using concentrated aspirate and enhanced cell-seeding efficiency onto allogeneic bone graft as an effect of osteoprogenitor concentration relative specifically to the concentration of erythrocytes in the aspirate.
  
  
  CONCLUSIONS
  These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing.
authors.affiliation: Bone and Joint Research Group, University of Southampton School of Medicine, York, UK.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Dawson
authors.forename: James O
authors.initials: JO
authors.lastname: Smith
authors.forename: Alexander
authors.initials: A
authors.lastname: Aarvold
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Ridgway
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Curran
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Dunlop
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001861:Bone Regeneration / Q000235:genetics; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D005374:Filtration; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis; D023822:Tissue Engineering