title: Regeneration of Vascularized Corticocancellous Bone and Diploic Space Using Muscle-Derived Stem Cells: A Translational Biologic Alternative for Healing Critical Bone Defects.
abstract: BACKGROUND
  Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing. This study investigates the utility of muscle-derived stem cells as a cellular therapy for definitive bone regeneration through a form of neo-osteogenesis.
  
  
  METHODS
  Adipose-derived stem cell, bone marrow-derived mesenchymal stem cell, and muscle-derived stem cell populations were isolated separately from C57BL/6 murine tissues and supplemented with collagen scaffolding with or without bone morphogenetic protein-2 to compare relative osteogenic potency and ultrastructure organization in both two- and three-dimensional systems. Parallel populations were bound to a deployable collagen implant within a syngeneic murine cranial defect model.
  
  
  RESULTS
  Although all populations provided and maintained mesenchymal stem cell multilineage capacity, adipose-derived stem cell- and bone marrow-derived mesenchymal stem cell-enriched constructs were capable of forming small bone aggregates. Defects receiving muscle-derived stem cells self-assembled a form of organized corticocancellous structures within two- and three-dimensional in vitro systems and within the in vivo model. Muscle-derived stem cells also augmented healing, implant angiogenesis, and diploic space formation.
  
  
  CONCLUSIONS
  Muscle-derived stem cell-enriched implants appear to provide an autologous response to current industry-derived products and an attractive alternative to mesenchymal stem cells for the regeneration of corticocancellous bone and a vascularized diploic space.
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Denver
authors.initials: D
authors.lastname: Lough
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Edward
authors.initials: E
authors.lastname: Swanson
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Sopko
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Christopher
authors.initials: C
authors.lastname: Madsen
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Devin
authors.initials: D
authors.lastname: Miller
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Howard
authors.initials: H
authors.lastname: Wang
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Srinivas M
authors.initials: SM
authors.lastname: Sursala
authors.affiliation: Baltimore, Md.|From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.
authors.forename: Anand R
authors.initials: AR
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D000071556:Cancellous Bone / Q000098:blood supply*; D000071538:Cortical Bone / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology*; D033581:Stem Cell Transplantation; D013234:Stem Cells; D014945:Wound Healing