European Journal of Cell Biology 85 (2006) 11–24 Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells Gerburg Keilhoff a,Ã , Alexander Goihl a , Kristina Langna¨se a , Hisham Fansa b , Gerald Wolf a a Institute of Medical Neurobiology, University of Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany b Department of Reconstructive and Aesthetic Surgery – Hand Surgery, Staedtische Kliniken, Teutoburger Strasse 50, D-33604 Bielefeld, Germany Received 20 July 2005; received in revised form 5 September 2005; accepted 21 September 2005 Abstract Bone marrow stromal cells (MSC) are multipotent stem cells that differentiate into cells of the mesodermal lineage. Although adult, their differentiation potential is remarkable, and they are able to transdifferentiate. Transdiffer- entiated cultivated rat MSC (tMSC) changed morphologically into cells resembling typical spindle-shaped Schwann cells (SC) with enhanced expression of LNGF receptor, Krox-20, CD104 and S100b protein and decreased expression of bone morphogenetic protein receptor-1A compared to untreated rat MSC (rMSC). Transdifferentiation was reversible and repeatable. To evaluate the myelinating capacity, rMSC, tMSC, or SC cultured from male rats were grafted into an autologous muscle conduit bridging a 2-cm gap in the female rat sciatic nerve. The presence of the male-specific SRY gene (as revealed by PCR analysis) and S100 immunoreactivity of pre-labeled tMSC confirmed the presence of the implanted cells in the grafts. Three weeks after grafting, an appropriate regeneration was noted in the SC and in the tMSC groups, while regeneration in the rMSC group and in the control group without any cells was impaired. In contrast to SC, in some cases, single tMSC were able to myelinate more than one axon. Our findings demonstrate that it may be possible to differentiate MSC into therapeutically useful cells for clinical applications. r 2005 Elsevier GmbH. All rights reserved. Keywords: Mesenchymal stem cell; Schwann cell; Transdifferentiation; Peripheral nerve; Nerve repair Introduction Myelinating cells, oligodendrocytes in the central nervous system (CNS), and Schwann cells (SC) in the peripheral nervous system (PNS) play a crucial role in neurodegenerative and regenerative processes. Demyeli- nating diseases in CNS and PNS and traumatic disorders lead to heavy functional impairment for the patients. One of the demyelinating diseases, multiple sclerosis (MS), a chronic autoimmune disease of the CNS, has a relatively high incidence and causes severe disabilities. Brain tissue of MS patients reveals sharply demarcated plaques in the CNS white matter with prevalence to the optic nerves and tracts of the periventricular regions. In these lesions, inflammatory infiltrates (specific T-cells, B-cells, macrophages, and microglia) are found together with immunological ARTICLE IN PRESS www.elsevier.de/ejcb 0171-9335/$ - see front matter r 2005 Elsevier GmbH. All rights reserved. doi:10.1016/j.ejcb.2005.09.021 Ã Corresponding author. Tel.: +49 391 671 4368; fax: +49 391 671 4365. E-mail address: gerburg.keilhoff@medizin.uni-magdeburg.de (G. Keilhoff).