title: Induction of fracture repair by mesenchymal cells derived from human embryonic stem cells or bone marrow.
abstract: Development of novel therapeutic approaches to repair fracture non-unions remains a critical clinical necessity. We evaluated the capacity of human embryonic stem cell (hESC)-derived mesenchymal stem/stromal cells (MSCs) to induce healing in a fracture non-union model in rats. In addition, we placed these findings in the context of parallel studies using human bone marrow MSCs (hBM-MSCs) or a no cell control group (n = 10-12 per group). Preliminary studies demonstrated that both for hESC-derived MSCs and hBM-MSCs, optimal induction of fracture healing required in vitro osteogenic differentiation of these cells. Based on biomechanical testing of fractured femurs, maximum torque, and stiffness were significantly greater in the hBM-MSC as compared to the control group that received no cells; values for these parameters in the hESC-derived MSC group were intermediate between the hBM-MSC and control groups, and not significantly different from the control group. However, some evidence of fracture healing was evident by X-ray in the hESC-derived MSC group. Our results thus indicate that while hESC-derived MSCs may have potential to induce fracture healing in non-unions, hBM-MSCs function more efficiently in this process. Additional studies are needed to further modify hESCs to achieve optimal fracture healing by these cells.
authors.affiliation: Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Undale
authors.forename: Daniel
authors.initials: D
authors.lastname: Fraser
authors.forename: Theresa
authors.initials: T
authors.lastname: Hefferan
authors.forename: Ross A
authors.initials: RA
authors.lastname: Kopher
authors.forename: James
authors.initials: J
authors.lastname: Herrick
authors.forename: Glenda L
authors.initials: GL
authors.lastname: Evans
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
authors.forename: Meredith
authors.initials: M
authors.lastname: Hayes
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Atkinson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.forename: Dan S
authors.initials: DS
authors.lastname: Kaufman
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002146:Bony Callus / Q000000981:diagnostic imaging; D002460:Cell Line; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000628:therapy*; D005347:Fibroblasts / Q000166:cytology; D017102:Fracture Healing / Q000502:physiology*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D011859:Radiography; D051381:Rats; D011923:Rats, Nude; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D014183:Transplantation, Heterologous