Original research| Volume 48, ISSUE 2, P163-169, March 2009

Mesenchymal Stem Cell Allograft in Revision Foot and Ankle Surgery: A Clinical and Radiographic Analysis

      A review was conducted of 23 patients who underwent implantation of mesenchymal stem cell allograft for revision foot or ankle surgery. Composed of viable mesenchymal stem cells derived from cadaveric donor tissue, the graft had osteogenic, osteoinductive, and osteoconductive properties, and was capable of direct new bone formation at the site of implantation. In all of the cases, radiographic new bone formation was observed at the area of implantation and a 91.3% union rate was observed, and no evidence of graft rejection or complications associated with implantation were recorded. Wilcoxon rank sum tests were used to determine whether gender, diabetes, chronic renal insufficiency, neuropathy, number of previous surgeries, and smoking were associated with time to healing. Spearman's rank correlation coefficient was calculated in an effort to identify the influence of continuous numeric variables on the time to bone healing. Based on the outcomes observed in this retrospective study, it appears that mesenchymal stem cell allograft is a beneficial biological adjunct to bone healing, and serves as a suitable bone autograft substitute in revision foot and ankle surgery. Level of Clinical Evidence: 4

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Foot and Ankle Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bruder S.P.
        • Fink D.J.
        • Caplan A.I.
        Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy.
        J Cell Biochem. 1994; 56: 283-294
        • Bruder S.P.
        • Kurth A.A.
        • Shea M.
        • Hayes W.C.
        • Jaiswal N.
        • Kadiyala S.
        Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells.
        J Orthop Res. 1998; 16: 155-162
        • Bruder S.P.
        • Kraus K.H.
        • Goldberg V.M.
        • Kadiyala S.
        The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects.
        J Bone Joint Surg Am. 1998; 80: 985-996
        • Younger E.M.
        • Chapman M.
        Morbidity at bone graft donor sites.
        J Orthop Trauma. 1989; 3: 192-195
        • Boden S.D.
        • Stevenson S.
        Modern issues in bone graft substitutes and advances in bone graft technology.
        Foot Ankle Clin. 2002; 7: 19-41
        • Brighton C.T.
        • Friedlaender G.E.
        • Lane J.M.
        Bone Formation and Repair.
        American Academy of Orthopaedic Surgeons, Rosemont, IL1994
        • Friedlaender G.E.
        • Goldberg V.M.
        Bone and Cartilage Allografts.
        American Academy of Orthopaedic Surgeons, Park Ridge, IL1990
        • Cook S.D.
        • Baffes G.C.
        • Wolfe M.W.
        • Sampath T.K.
        • Rueger D.C.
        Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model.
        Clin Orthop Relat Res. 1994; 301: 302-312
        • Cook S.D.
        • Dalton J.E.
        • Tan E.H.
        • Whitecloud 3rd, T.S.
        • Rueger D.C.
        In vivo evaluation of recombinant human osteogenic protein (rhOP-1) implants as a bone graft substitute for spinal fusions.
        Spine. 1994; 19: 1655-1663
        • Cook S.D.
        • Rueger D.C.
        Osteogenic protein-1: biology and applications.
        Clin Orthop Relat Res. 1996; 324: 29-38
        • Cook S.D.
        • Wolfe M.W.
        • Salkeld S.L.
        • Rueger D.C.
        Effect of recombinant human osteogenic protein-1 on healing of segmental defects in nonhuman primates.
        J Bone Joint Surg Am. 1995; 77: 734-750
        • Cunningham B.W.
        • Kanayama M.
        • Parker L.M.
        • Weis J.C.
        • Sefter J.C.
        • Fedder I.L.
        • McAfee P.C.
        Osteogenic protein versus autologous interbody arthrodesis in sheep thoracic spine.
        Spine. 1999; 24: 509-518
        • Geesink R.G.
        • Hoefnagels N.H.
        • Bulstra S.K.
        Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect.
        J Bone Joint Surg Br. 1999; 81: 710-718
        • Grauer J.N.
        • Patel T.C.
        • Erulkar J.S.
        • Troiano N.W.
        • Panjabi M.M.
        • Friedlaender G.E.
        Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion.
        Spine. 2001; 26: 127-133
        • Caplan A.I.
        Mesenchymal stem cells.
        J Orthop Res. 1991; 9: 641-650
        • Bruder S.P.
        • Jaiswal N.
        • Haynesworth S.E.
        Growth kinetics, self-renewal and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation.
        J Cell Biochem. 1997; 64: 278-294
        • Beresford J.N.
        Osteogenic stem cells and the stromal system of bone and marrow.
        Clin Orthop Relat Res. 1989; 240: 270-280
        • Caplan A.I.
        Mesenchymal stem cells: cell-based reconstructive therapy in orthopedics.
        Tissue Eng. 2005; 11: 1198-1211
        • Caplan A.I.
        The mesengenic process.
        Clin Plast Surg. 1994; 21: 429-435
        • Dennis J.E.
        • Caplan A.I.
        Advances in mesenchymal stem cell biology.
        Curr Opin Orthop. 2004; 15: 341-346
        • Friedenstein A.J.
        • -Shapiro II, Piatetzky
        • Petrakova K.V.
        Osteogenesis in transplants of bone marrow cells.
        J Embryol Exp Morphol. 1996; 16: 381-390
        • Le Blanc K.
        • Götherström C.
        • Ringdén O.
        • Hassan M.
        • McMahon R.
        • Horwitz E.
        • Anneren G.
        • Axelsson O.
        • Nunn J.
        • Ewald U.
        • Nordén-Lindeberg S.
        • Jansson M.
        • Dalton A.
        • Aström E.
        • Westgren M.
        Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.
        Transplantation. 2005; 79: 1607-1614
        • Risbud M.V.
        • Shapiro I.M.
        • Guttapalli A.
        • Di Martino A.
        • Danielson K.G.
        • Beiner J.M.
        • Hillibrand A.
        • Albert T.J.
        • Anderson D.G.
        • Vaccaro A.R.
        Osteogenic potential of adult human stem cells of the lumbar vertebral body and the iliac crest.
        Spine. 2006; 31: 83-89
        • Livingston T.L.
        • Gordon S.
        • Archambault M.
        • Kadiyala S.
        • McIntosh K.
        • Smith A.
        • Peter S.J.
        Mesenchymal stem cells combined with biphasic calcium phosphate ceramics promote bone regeneration.
        J Mater Sci Mater Med. 2003; 14: 211-218
        • Kadiyala S.
        • Jaiswal N.
        • Bruder S.P.
        Culture-expanded, bone marrow-derived mesenchymal stem cells can regenerate a critical-sized segmental bone defect.
        Tissue Eng. 1997; 3: 173-185
        • Hayflick L.
        The limited in vitro lifetime of human diploid strains.
        Exp Cell Res. 1965; 37: 614-636
        • Muschler G.F.
        • Nitto H.
        • Boehm C.A.
        • Easley K.A.
        Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors.
        J Orthop Res. 2001; 19: 117-125
        • Majors A.K.
        • Boehm C.A.
        • Nitto H.
        • Midura R.J.
        • Muschler G.F.
        Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation.
        J Orthop Res. 1997; 15: 546-557
        • Muschler G.F.
        • Nitto H.
        • Matsukura Y.
        • Boehm C.
        • Valdevit A.
        • Kambic H.
        • Davros W.
        • Powell K.
        • Easley K.
        Spine fusion using cell matrix composites enriched in bone marrow-derived cells.
        Clin Orthop Relat Res. 2003; 407: 102-118
        • Connolly J.F.
        • Guse R.
        • Tiedeman J.
        • Dehne R.
        Autologous marrow injection as a substitute for operative grafting of tibial nonunions.
        Clin Orthop Relat Res. 1991; 266: 259-270
        • Horwitz E.M.
        • Prockop D.J.
        • Fitzpatrick L.A.
        • Koo W.W.
        • Gordon P.L.
        • Neel M.
        • Sussman M.
        • Orchard P.
        • Marx J.C.
        • Pyeritz R.E.
        • Brenner M.K.
        Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta.
        Nat Med. 1999; 5: 309-313
      1. Togawa D, Lieberman I, McLain R, Richmond B, Fleming J Jr, Reinhardt M, Boehm C, Muschler G. Lumbar interbody fusion using allograft enriched with bone marrow derived cells prepared by selective stem cell retention—results of clinical and radiographic studies and in-vitro assay. Paper presented at: Annual Meeting of the North American Spine Society; October 26–30, 2004; Chicago, IL.

        • Muschler G.F.
        • Boehm C.
        • Easley K.
        Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume.
        J Bone Joint Surg Am. 1997; 79 (Erratum in: J Bone Joint Surg Am 80:302, 1998): 1699-1709
        • Bergman R.J.
        • Gazit D.
        • Kahn A.J.
        • Gruber H.
        • McDougall S.
        • Hahn T.J.
        Age-related changes in osteogenic stem cell in mice.
        J Bone Miner Res. 1996; 11: 568-577
        • noue K.
        • Ohgushi H.
        • Yoshikawa T.
        • Okumura M.
        • Sempuku T.
        • Tamai S.
        • Dohi Y.
        The effect of aging on bone formation in porous hydroxyapatite: biochemical and histological analysis.
        J Bone Miner Res. 1997; 12: 989-994
        • Liang C.T.
        • Barnes J.
        • Seedor J.G.
        • Quartuccio H.A.
        • Bolander M.
        • Jeffrey J.J.
        • Rodan G.A.
        Impaired bone activity in rats: alterations at the cellular and molecular levels.
        Bone. 1992; 13: 435-441
        • Quarto R.
        • Thomas D.
        • Liang C.T.
        Bone progenitor cell deficits and age-associated decline in bone repair capacity.
        Calcif Tissue Int. 1995; 56: 123-129
        • Tabuchi C.
        • Simmons D.J.
        • Fausto A.
        • Russell J.E.
        • Binderman I.
        • Avioli L.V.
        Bone deficit in ovariectomized rats.
        J Clin Invest. 1986; 78: 637-642
        • Tsuji T.
        • Hughes F.J.
        • McCulloch C.A.
        • Melcher A.H.
        Effect of donor age on osteogenic cells of rat bone marrow in vitro.
        Mech Ageing Dev. 1990; 51: 121-132
        • Hernigou P.
        • Mathieu G.
        • Poignard A.
        • Manicom O.
        • Beaujean F.
        • Rouard H.
        Percutaneous autologous bone-marrow grafting for nonunions.
        J Bone Joint Surg Am. 2006; 88: 322-327
        • McLain R.F.
        • Fleming J.E.
        • Boehm C.A.
        • Muschler G.F.
        Aspiration of osteoprogenitor cells for augmentation in spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest.
        J Bone Joint Surg Am. 2005; 87: 2655-2661