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Autologous cell-based therapy for treatment of large bone defects: from bench to bedside

Journal

EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
Volume 44, Issue 5, Pages 649-665

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00068-018-0906-y

Keywords

Bone defect; Cell therapy; Stem cells; BMC; Bone marrow mononuclear cells; Regeneration

Funding

  1. LOEWE Center for Cell and Gene Therapy Frankfurt - Hessisches Ministerium fur Wissenschaft und Kunst (HMWK
  2. Hessian Ministry of Higher Education, Research and the Arts) [III L 4-518/17.004 [2010]]
  3. AO [05-S23, S-10-47-H, S-11-64-N]
  4. German Institute for Cell and Tissue Replacement gGmbH (DIZG, Berlin)

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ObjectivesReconstruction of long segmental bone defects is demanding for patients and surgeons, and associated with long-term treatment periods and substantial complication rates in addition to high costs. While defects up to 4-5 cm length might be filled up with autologous bone graft, heterologous bone from cadavers, or artificial bone graft substitutes, current options to reconstruct bone defects greater than 5 cm consist of either vascularized free bone transfers, the Masquelet technique or the Ilizarov distraction osteogenesis. Alternatively, autologous cell transplantation is an encouraging treatment option for large bone defects as it eliminates problems such as limited autologous bone availability, allogenic bone immunogenicity, and donor-site morbidity, and might be used for stabilizing loose alloplastic implants.MethodsThe authors show different cell therapies without expansion in culture, with ex vivo expansion and cell therapy in local bone defects, bone healing and osteonecrosis. Different kinds of cells and scaffolds investigated in our group as well as in vivo transfer studies and BMC used in clinical phase I and IIa clinical trials of our group are shown.ResultsOur research history demonstrated the great potential of various stem cell species to support bone defect healing. It was clearly shown that the combination of different cell types is superior to approaches using single cell types. We further demonstrate that it is feasible to translate preclinically developed protocols from in vitro to in vivo experiments and follow positive convincing results into a clinical setting to use autologous stem cells to support bone healing.

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