Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve |
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| Authors: | Fátima Rosalina Pereira Lopes Flávia Frattini Suelen Adriani Marques Fernanda Martins de Almeida Lenira Camargo de Moura Campos Francesco Langone Silvano Lora Radovan Borojevic Ana Maria Blanco Martinez |
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| Institution: | 1. Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil;2. Departamento de Patologia da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil;3. Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Brazil;4. Departamento de Fisiologia e Biofísica, Universidade Estadual de Campinas, São Paulo, Brazil;5. Instituto per la Sintesi Orgânica e la Fotoreatività, CNR, Legnaro-Padova, Italy;6. APABCAM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil;1. Department of Trauma and Orthopaedics, Peking University People’s Hospital, Beijing, PR China;2. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, PR China;1. Hypoxia and Therapeutics Group, Manchester Pharmacy School, University of Manchester, UK;2. Experimental and Clinical Endocrinology, Medizinische Klinik I, Lübeck, Germany;1. Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany;2. Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany;3. Werner-Reichardt-Centre for Integrative Neuroscience, Eberhard-Karls-University, 72076 Tuebingen, Germany;1. Service de chirurgie plastique et reconstructrice de l’appareil locomoteur, centre chirurgical Emile-Gallé, CHU de Nancy, 54000 Nancy, France;2. Département de chirurgie orthopédique et de traumatologie, hôpital Purpan, CHU de Toulouse, place du Dr-Baylac, 31059 Toulouse cedex, France;1. School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074, China;2. School of Power and Mechanical Engineering, Wuhan University, Wuhan 430072, China;1. Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland;2. Faculty of Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland |
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| Abstract: | Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model. |
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