Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation |
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| Authors: | Jonne Tikkanen Hannu-Ville Leskelä Siri T Lehtonen Vesa Vähäsarja Jukka Melkko Lauri Ahvenjärvi Eija Pääkkö Kalervo Väänänen Petri Lehenkari |
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| Institution: | 1. Department of Surgery, Clinical Research Center, Oulu University Hospital, Oulu, Finland;2. Department of Biomedicine, Division of Anatomy and Cell Biology, University of Oulu, Oulu, Finland;3. Department of Pediatrics, Oulu University Hospital, Oulu, Finland;4. Department of Pathology, Oulu University Hospital, Oulu, Finland;5. Department of Radiology, Oulu University Hospital, Oulu, Finland;6. University of Eastern Finland, Kuopio, Finland;1. Université de Lyon, CNRS, INSA-Lyon, LIRIS, UMR5205, F-69621, Villeurbanne, France;2. Université de Savoie, CNRS, LAMA, UMR 5127, F-73776, Chambéry, France;3. Université Grenoble-Alpes, CNRS, LJK, UMR 5224, F-38041, Grenoble, France;1. Department of Applied Mathematics, Northwestern Polytechnical University, Xian 710072, PR China;2. Computational and Theoretical Neuroscience Laboratory, Institute for Telecommunications Research, University of South Australia, SA 5095, Australia;1. Graduate School of Bio- and Nanosystem Sciences, Yokohama City University, Yokohama 236-0027, Japan;2. Department of Chemistry, School of Chemical Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;3. Yokohama College of Pharmacy, Yokohama 245-0066, Japan;1. Department of Neurosurgery, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Gwangju, South Korea;2. Department of Radiation Oncology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Gwangju, South Korea;3. Department of Pathology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Gwangju, South Korea;4. Department of Radiology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, South Korea;1. Physics Group, Qazvin Branch, Islamic Azad University, Qazvin, Iran;2. Department of Physics, University of Zanjan, Zanjan 45195-313, Iran;3. Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;1. International Islamic University Malaysia, Kuala Lumpur, Malaysia;2. Nottingham University Business School, The University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia |
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| Abstract: | Background aimsCongenital pseudarthrosis of the tibia (CPT) caused by neurofibromatosis type 1 (NF1) is a refractory disease occurring in childhood. We present two cases that had failed all earlier treatment attempts and, as a last treatment attempt, the patients were chosen to receive mesenchymal stromal cell (MSC) transplantation prior to amputation.MethodsThe MSC from bone marrow (BM) were harvested from the iliac crest and cultured in osteoinductive medium for 3 weeks. The cultured MSC were injected in solution into BM canals of the tibia and around the resection line or bone defect in a 3-dimensional collagen sponge scaffold. After the MSC transplantation, the patients were monitored during a 10-month follow-up period. In both cases, bone formation at the pseudarthrosis site was observed and two of three treated bone defects healed. For clinical reasons not related to cell transplantation, such as new infection and pseudarthrosis and severe shortening of the leg, both extremities were finally amputated and bone samples were analyzed to evaluate MSC therapy effect and safety.ResultsMSC transplantation normalized bone remodeling, promoted bone resorption and improved the overall structure of bone. The number of osteoclasts in the cortical bone was 2-fold higher compared with the monitored situation before MSC transfer. In addition, the mineral content of the bone improved after transplantation. We could see no sign of aberrant bone formation or malignant transformation.ConclusionsOur data suggest that MSC transplantation is a possibility for treatment of CPT caused by NF1 in less severe cases without adjunct defects. |
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