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

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.

• Publication year

  2018

• Venue

  European Journal of Trauma and Emergency Surgery

• Publication date

  2018-01-19

• Fields of study

  Medicine

• Identifiers
  DOI 10.1007/s00068-018-0906-yPMID 29352347PMCID 6182650
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Comparison of three different types of scaffolds preseeded with human bone marrow mononuclear cells on the bone healing in a femoral critical size defect model of the athymic rat

  2018cited by this paper
• Safety and feasibility of cell-based therapy of autologous bone marrow-derived mononuclear cells in plate-stabilized proximal humeral fractures in humans

  2016cited by this paper
• Effect of the harvest procedure and tissue site on the osteogenic function of and gene expression in human mesenchymal stem cells

  2016cited by this paper
• Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First‐in‐Man Study

  2016cited by this paper
• Percutaneous injection of bone marrow mesenchymal stem cells for ankle non-unions decreases complications in patients with diabetes

  2015cited by this paper
• Cell-Based Therapy by Implanted Human Bone Marrow-Derived Mononuclear Cells Improved Bone Healing of Large Bone Defects in Rats

  2015cited by this paper
• In vivo comparison of hard tissue regeneration with ovine mesenchymal stem cells processed with either the FICOLL method or the BMAC method.

  2015cited by this paper
• Improved Bone Formation by Differentiated Mesenchymal Stem Cells and Endothelial Progenitor Cells Seeded on High Concentrated Bioglass-Polylactic Acid Composite in Calvarial Rat Bone Defect

  2015cited by this paper
• Bone Mesenchymal Stem Cells with Growth Factors Successfully Treat Nonunions and Delayed Unions

  2015cited by this paper
• Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro

  2015cited by this paper
• Follow-Up of Implant Survival Comparing Ficoll and Bone Marrow Aspirate Concentrate Methods for Hard Tissue Regeneration with Mesenchymal Stem Cells in Humans

  2014cited by this paper
• Bone Marrow Aspirate Concentrate and Platelet-rich Plasma Enhanced Bone Healing in Distraction Osteogenesis of the Tibia

  2014cited by this paper
• Bone Marrow Aspirate Concentrate and Platelet-rich Plasma Enhanced Bone Healing in Distraction Osteogenesis of the Tibia

  2014cited by this paper
• Bone augmentation with TiMesh. autologous bone versus autologous bone and bone substitutes. A systematic review.

  2014cited by this paper
• Human Endothelial-Like Differentiated Precursor Cells Maintain Their Endothelial Characteristics When Cocultured with Mesenchymal Stem Cell and Seeded onto Human Cancellous Bone

  2013cited by this paper
• Percutaneous autogenous bone marrow injection for delayed union or non union of fractures after internal fixation.

  2013cited by this paper
• High Calcium Bioglass Enhances Differentiation and Survival of Endothelial Progenitor Cells, Inducing Early Vascularization in Critical Size Bone Defects

  2013cited by this paper
• Endothelial Progenitor Cells Improve Directly and Indirectly Early Vascularization of Mesenchymal Stem Cell-Driven Bone Regeneration in a Critical Bone Defect in Rats

  2012cited by this paper
• Regenerate augmentation with bone marrow concentrate after traumatic bone loss

  2012cited by this paper
• Safety of Mesenchymal Stem Cells for Clinical Application

  2012cited by this paper
• IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein.

  2012cited by this paper
• Single-platform quality control assay to quantify multipotential stromal cells in bone marrow aspirates prior to bulk manufacture or direct therapeutic use.

  2012cited by this paper
• Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy

  2011cited by this paper
• Mesenchymal stromal cells derived from CD271(+) bone marrow mononuclear cells exert potent allosuppressive properties.

  2011cited by this paper
• Bridging the gap: Bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects

  2011cited by this paper
• CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization.

  2011influential reference
• CD133+CD34+ stem cells are mobilized after musculoskeletal surgery and target endothelium activated by surgical wound fluid

  2011cited by this paper
• Mesenchymal stem cell (MSC) and endothelial progenitor cell (EPC) growth and adhesion in six different bone graft substitutes

  2011cited by this paper
• Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review.

  2011cited by this paper
• Masquelet technique for the treatment of bone defects: tips-tricks and future directions.

  2011cited by this paper
• Trauma-Activated Polymorphonucleated Leukocytes Damage Endothelial Progenitor Cells: Probable Role of CD11b/CD18-CD54 Interaction and Release of Reactive Oxygen Species

  2011cited by this paper
• Autologous bone grafting on steroids: preliminary clinical results. A novel treatment for nonunions and segmental bone defects

  2011cited by this paper
• RIA reamings and hip aspirate: a comparative evaluation of osteoprogenitor and endothelial progenitor cells.

  2010influential reference
• Endothelial Progenitor Cells and Mesenchymal Stem Cells Seeded onto β-TCP Granules Enhance Early Vascularization and Bone Healing in a Critical-Sized Bone Defect in Rats

  2010cited by this paper
• Epigenetic remodeling of chromatin architecture: exploring tumor differentiation therapies in mesenchymal stem cells and sarcomas.

  2010cited by this paper
• Bone-marrow-derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head: a preliminary study.

  2010cited by this paper
• Surgical Wound Fluid From Elderly Patients Shows a Dramatically Reduced Potential to Stimulate In-vitro Recruitment and Differentiation of Endothelial Progenitor Cells: Role of VEGF-165 and TGF-β1.

  2010cited by this paper
• Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

  2010cited by this paper
• Cell therapy in bone healing disorders

  2010cited by this paper
• CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties

  2010cited by this paper
• Spinning around or stagnation - what do osteoblasts and chondroblasts really like?

  2010cited by this paper
• Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro.

  2010cited by this paper
• Treatment of nontraumatic osteonecrosis of the femoral head with the implantation of core decompression and concentrated autologous bone marrow containing mononuclear cells

  2010cited by this paper
• Repair of bone defect using bone marrow cells and demineralized bone matrix supplemented with polymeric materials.

  2010cited by this paper
• Gelenkerhaltende Operationen bei atraumatischer Femurkopfnekrose

  2010cited by this paper
• Atraumatische Femurkopfnekrose des Erwachsenen

  2010cited by this paper
• [Our first experiences with autologous transplantation of bone marrow stem cells to treat pseudarthrosis, delayed fracture healing and long bone defects fracture].

  2009cited by this paper
• One-step Bone Marrow-derived Cell Transplantation in Talar Osteochondral Lesions

  2009cited by this paper
• Properties and growth of human bone marrow mesenchymal stromal cells cultivated in different media.

  2009cited by this paper
• Efficacy of aspiration and autogenous bone marrow injection in the treatment of simple bone cysts

  2009cited by this paper
• Endothelial progenitor cells – hype or hope?

  2009cited by this paper
• Differential Effects of Culture-expanded Bone Marrow Cells on the Regeneration of Bone Between the Femoral and the Tibial Lengthenings

  2009cited by this paper
• Bone marrow concentrate: a novel strategy for bone defect treatment.

  2009cited by this paper
• Self-Assembling Peptide Nanofiber Scaffolds, Platelet-Rich Plasma, and Mesenchymal Stem Cells for Injectable Bone Regeneration With Tissue Engineering

  2009cited by this paper
• Cell therapy of hip osteonecrosis with autologous bone marrow grafting

  2009cited by this paper
• Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients

  2009cited by this paper
• A randomized clinical trial comparing intralesional bone marrow and steroid injections for simple bone cysts.

  2008cited by this paper
• Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum.

  2008cited by this paper
• Tissue engineering of bone: material and matrix considerations.

  2008cited by this paper
• Tissue engineering for bone defect healing: an update on a multi-component approach.

  2008cited by this paper
• A Study of 23 Unicameral Bone Cysts of the Calcaneus: Open Chip Allogeneic Bone Graft versus Percutaneous Injection of Bone Powder with Autogenous Bone Marrow

  2008cited by this paper
• The clinical use of enriched bone marrow stem cells combined with porous beta-tricalcium phosphate in posterior spinal fusion.

  2008cited by this paper
• Number and Proliferative Capacity of Human Mesenchymal Stem Cells Are Modulated Positively in Multiple Trauma Patients and Negatively in Atrophic Nonunions

  2007cited by this paper
• Percutaneous reaming of simple bone cysts in children followed by injection of demineralized bone matrix and autologous bone marrow.

  2007cited by this paper
• Zellbasierte Therapie der Femurkopfnekrose

  2007cited by this paper
• Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

  2007cited by this paper
• Fracture healing: the diamond concept.

  2007cited by this paper
• Is It Possible to Obtain “True Endothelial Progenitor Cells” by In Vitro Culture of Bone Marrow Mononuclear Cells?

  2007cited by this paper
• High dosage of simvastatin reduces TNF-alpha-induced apoptosis of endothelial progenitor cells but fails to prevent apoptosis induced by IL-1beta in vitro.

  2007cited by this paper
• [Treatment of bone cyst by transplantation of autologous bone marrow combined with allograft bone].

  2007cited by this paper
• High Dosage of Simvastatin Reduces TNF-α-Induced Apoptosis of Endothelial Progenitor Cells but Fails to Prevent Apoptosis Induced by IL-1β In Vitro

  2007cited by this paper
• Surgical Technique Percutaneous Autologous Bone-Marrow Grafting for Nonunions.

  2007cited by this paper
• Additive effect of endothelial progenitor cell mobilization and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs.

  2007cited by this paper
• [Cell based therapy for the treatment of femoral head necrosis].

  2007cited by this paper
• Microvessel-Like Structures from Outgrowth Endothelial Cells from Human Peripheral Blood in 2-Dimensional and 3-Dimensional Co-Cultures with Osteoblastic Lineage Cells

  2007cited by this paper
• Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique.

  2006cited by this paper
• Cartilage repair: generations of autologous chondrocyte transplantation.

  2006cited by this paper
• Treatment of osteonecrosis of the femoral head by percutaneous decompression and autologous bone marrow mononuclear cell infusion.

  2006cited by this paper
• Abstract 3685: Intracoronary Infusion of Bone-Marrow-Derived Progenitor Cells is Associated with Improved Clinical Outcome in Patients with Acute Myocardial Infarction: 12 Months Follow Up of the REPAIR-AMI Trial

  2006cited by this paper
• Healos and Bone Marrow Aspirate Used for Lumbar Spine Fusion: A Case Controlled Study Comparing Healos With Autograft

  2006cited by this paper
• Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture

  2006influential reference
• Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation.

  2006cited by this paper
• Percutaneous Autologous Bone-Marrow Grafting for Nonunions

  2005cited by this paper
• Early postoperative adherence of matrix-induced autologous chondrocyte implantation for the treatment of full-thickness cartilage defects of the femoral condyle

  2005cited by this paper
• Human reaming debris: a source of multipotent stem cells.

  2005cited by this paper
• Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells.

  2005cited by this paper
• Percutaneous Reaming of Simple Bone Cysts in Children Followed by Injection of Demineralized Bone Matrix and Autologous Bone Marrow

  2005cited by this paper
• Serum Derived from Multiple Trauma Patients Promotes the Differentiation of Endothelial Progenitor Cells In Vitro: Possible Role of Transforming Growth Factor-&bgr;1 and Vascular Endothelial Growth Factor165

  2004cited by this paper
• Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study.

  2004cited by this paper
• Comparison of Bone Grafts for Posterior Spinal Fusion in Adolescent Idiopathic Scoliosis

  2003cited by this paper
• Influence of Different Culture Solutions on Osteoblastic Differentiation in Cord Blood and Bone Marrow Derived Progenitor Cells. Einfluß verschiedener Kulturnährmedien auf das osteoblastäre Differenzierungsverhalten von Progenitorzellen aus Knochenmark und Nabelschnurblut

  2003cited by this paper
• Treatment of Simple Bone Cysts With Aspiration and a Single Bone Marrow Injection

  2003cited by this paper
• Unicameral bone cysts treated by injection of bone marrow or methylprednisolone.

  2002cited by this paper
• Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI)

  2002cited by this paper
• Treatment of Osteonecrosis With Autologous Bone Marrow Grafting

  2002cited by this paper
• Improvement of fracture healing by systemic administration of growth hormone and local application of insulin-like growth factor-1 and transforming growth factor-beta1.

  2002cited by this paper
• Treatment of Active Unicameral Bone Cysts with Percutaneous Injection of Demineralized Bone Matrix and Autogenous Bone Marrow

  2002cited by this paper
• Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats.

  2001cited by this paper
• Increase in Circulating Endothelial Progenitor Cells by Statin Therapy in Patients With Stable Coronary Artery Disease

  2001cited by this paper
• Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors.

  2000cited by this paper

• The use of autologous biomaterials in combination with biocompatible matrices for restoration of bone tissue defects (literature review)

  2025cites this paper
• The Genetic and Biological Basis of Pseudoarthrosis in Fractures: Current Understanding and Future Directions

  2025cites this paper
• Efficacy of mesenchymal stem cell-based therapy on the bone repair of hypertensive rats.

  2024cites this paper
• Research progress of gene therapy combined with tissue engineering to promote bone regeneration

  2024cites this paper
• Impact of 3D Printing Techniques on Bone Reconstruction: Systematic review and Descriptive Study

  2024cites this paper
• Porous Biocoatings Based on Diatomite with Incorporated ZrO2 Particles for Biodegradable Magnesium Implants

  2023cites this paper
• Cellularity in bone marrow autografts for bone and fracture healing.

  2023cites this paper
• Comparing the Benefits and Drawbacks of Stem Cell Therapy Based on the Cell Origin or Manipulation Process: Addressing Immunogenicity

  2023influential citation
• Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study

  2023cites this paper
• Surgical suction filter-derived bone graft displays osteogenic miRNA and mRNA patterns

  2023influential citation
• Feasibility evaluation of the induced membrane technique with structural autologous strip bone graft management of phalangeal and metacarpal segmental defects using radiography

  2023cites this paper
• Human Mesenchymal Stem Cells and Innovative Scaffolds for Bone Tissue Engineering Applications

  2023cites this paper
• One Stage Masquelets Technique: Evaluation of Different Forms of Membrane Filling with and without Bone Marrow Mononuclear Cells (BMC) in Large Femoral Bone Defects in Rats

  2023cites this paper
• Knochenaufbau und Knochenersatzmaterialien

  2022cites this paper
• Delivery of bone morphogenetic protein-2 by crosslinking heparin to nile tilapia skin collagen for promotion of rat calvaria bone defect repair

  2022cites this paper
• Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ

  2022cites this paper
• Biomimicry in nanotechnology: a comprehensive review

  2022cites this paper
• Issues with Tissues: Trends in Tissue-Engineered Products in Clinical Trials in the European Union

  2022cites this paper
• Application of three-dimensional bioprinting technology in orthopedics

  2022cites this paper
• The Induced Membrane Technique—The Filling Matters: Evaluation of Different Forms of Membrane Filling with and without Bone Marrow Mononuclear Cells (BMC) in Large Femoral Bone Defects in Rats

  2022cites this paper
• In vivo behaviors of highly flexible paper consisting of ultralong hydroxyapatite nanowires.

  2021cites this paper
• Cell therapy: A potential solution for the healing of bone cavities

  2021cites this paper
• The efficiency of internal fixation with bone grafting at docking sites after bone transport for treatment of large segmental tibial bone defects.

  2021cites this paper
• Biomimetics and Its Influence in Plastic and Reconstructive Surgery

  2021cites this paper
• Surface treatment of 3D printed porous Ti6Al4V implants by ultraviolet photofunctionalization for improved osseointegration

  2021cites this paper
• Panax notoginseng Saponin Promotes Bone Regeneration in Distraction Osteogenesis via the TGF-β1 Signaling Pathway

  2021cites this paper
• Fibrous Demineralized Bone Matrix (DBM) Improves Bone Marrow Mononuclear Cell (BMC)-Supported Bone Healing in Large Femoral Bone Defects in Rats

  2021cites this paper
• Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

  2021cites this paper
• Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

  2021cites this paper
• Comparison between Tonifying Kidney Yang and Yin in Treating Segmental Bone Defects Based on the Induced Membrane Technique: An Experimental Study in a Rat Model

  2020cites this paper
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  2020cites this paper
• Reconstruction of Large Skeletal Defects: Current Clinical Therapeutic Strategies and Future Directions Using 3D Printing

  2020cites this paper
• Electrical stimulation in bone tissue engineering treatments

  2020cites this paper
• Effect of olfactory ensheathing cells combined with chitosan on inhibition of P2×4 receptor over-expression-mediated neuropathic pain.

  2020cites this paper
• Determination of the effective dose of bone marrow mononuclear cell therapy for bone healing in vivo

  2020cites this paper
• 3D-Printing of Hierarchically Designed and Osteoconductive Bone Tissue Engineering Scaffolds

  2020cites this paper
• Regeneration of segmental defects in metatarsus of sheep with vascularized and customized 3D-printed calcium phosphate scaffolds

  2020cites this paper
• Introduction of a New Surgical Method to Improve Bone Healing in a Large Bone Defect by Replacement of the Induced Membrane by a Human Decellularized Dermis Repopulated with Bone Marrow Mononuclear Cells in Rat

  2020cites this paper
• Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion: Problems solved and unsolved.

  2020cites this paper
• First Human Leucocyte Antigen (HLA) Response and Safety Evaluation of Fibrous Demineralized Bone Matrix in a Critical Size Femoral Defect Model of the Sprague-Dawley Rat

  2020cites this paper
• Enrichment and preserved functionality of multipotential stromal cells in bone marrow concentrate processed by vertical centrifugation.

  2020cites this paper
• Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment

  2020cites this paper
• Treatment of simple bone cysts of humerus by intramedullary decompression and drainage with elastic stable intramedullary nailing combined with intralesional injections of steroids

  2019cites this paper
• Nonunions of the humerus – Treatment concepts and results of the last five years

  2019cites this paper
• Bone stock reconstruction for huge bone loss using allograft-bones, bone marrow, and teriparatide in an infected total knee arthroplasty.

  2019cites this paper
• Innovative Biomaterials for Bone Regrowth

  2019cites this paper
• Focus on non-union of fractures

  2019cites this paper
• Treatment of simple bone cysts of the humerus by intramedullary nailing and steroid injection

  2019cites this paper
• Improved osseointegration with rhBMP-2 intraoperatively loaded in a specifically designed 3D-printed porous Ti6Al4V vertebral implant.

  2019cites this paper
• Comparison between the induced membrane technique and distraction osteogenesis in treating segmental bone defects: An experimental study in a rat model

  2019cites this paper
• Role of Adult Tissue-Derived Pluripotent Stem Cells in Bone Regeneration

  2019cites this paper
• Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview

  2019cites this paper
• Adult Stem Cells for Bone Regeneration and Repair

  2019cites this paper
• Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur.

  2019cites this paper
• University of Southern Denmark TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38

  2019cites this paper
• Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway

  2019cites this paper
• Influence of the incorporation of marine spongin into a Biosilicate®: an in vitro study

  2019cites this paper
• Translational research: what is the value of experimental studies in comparison with clinical studies to help understand clinical problems?

  2018cites this paper
• Influence of concentration and preparation of platelet rich fibrin on human bone marrow mononuclear cells (in vitro)

  2018cites this paper
• Effect of bone marrow stromal cells in combination with biomaterials in early phases of distraction osteogenesis: An experimental study in a rabbit femur model.

  2018cites this paper
• TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1‐p38 Signaling

  2018cites this paper