title: Positive selection for bone morphogenetic protein receptor type-IB promotes differentiation and specification of human adipose-derived stromal cells toward an osteogenic lineage.
abstract: BACKGROUND
  Adipose tissue represents an abundant and easily accessible source of multipotent cells that may serve as an excellent building block for tissue engineering. However, adipose-derived stromal cells (ASCs) are a heterogeneous group and subpopulations may be identified with enhanced osteogenic potential.
  
  
  METHODS
  Human ASC subpopulations were prospectively isolated based on expression of bone morphogenetic protein receptor type-IB (BMPR-IB). Unsorted, BMPR-IB(+), and BMPR-IB(-) cells were analyzed for their osteogenic capacity through histological staining and gene expression. To evaluate their in vivo osteogenic potential, critical-sized calvarial defects were created in immunocompromised mice and treated with unsorted, BMPR-IB(+), or BMPR-IB(-) cells. Healing was assessed using microcomputed tomography and pentachrome staining of specimens at 8 weeks.
  
  
  RESULTS
  Increased osteogenic differentiation was noted in the BMPR-IB(+) subpopulation, as demonstrated by alkaline phosphatase staining at day 7 and extracellular matrix mineralization with Alizarin red staining at day 14. This was also associated with increased expression for osteocalcin, a late marker of osteogenesis. Radiographic analysis demonstrated significantly enhanced healing of critical-sized calvarial defects treated with BMPR-IB(+) ASCs compared with unsorted or BMPR-IB(-) cells. This was confirmed through pentachrome staining, which revealed more robust bone regeneration in the BMPR-IB(+) group.
  
  
  CONCLUSIONS
  BMPR-IB(+) human ASCs have an enhanced ability to form bone both in vitro and in vivo. These data suggest that positive selection for BMPR-IB(+) and manipulation of the BMP pathway in these cells may yield a highly osteogenic subpopulation of cells for bone tissue engineering.
authors.affiliation: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine , Stanford, California.
authors.forename: Adrian
authors.initials: A
authors.lastname: McArdle
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Paik
authors.forename: Chris
authors.initials: C
authors.lastname: Duldulao
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.forename: Robert
authors.initials: R
authors.lastname: Rennert
authors.forename: Graham G
authors.initials: GG
authors.lastname: Walmsley
authors.forename: Kshemendra
authors.initials: K
authors.lastname: Senarath-Yapa
authors.forename: Michael
authors.initials: M
authors.lastname: Hu
authors.forename: Elly
authors.initials: E
authors.lastname: Seo
authors.forename: Min
authors.initials: M
authors.lastname: Lee
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Wan
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D000328:Adult; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D010012:Osteogenesis / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I