Research Paper Tissue Regeneration The use of undifferentiated bone marrow stromal cells for sciatic nerve regeneration in rats R. Mohammadi, S. Azizi, N. Delirezh, R. Hobbenaghi, K. Amini, P. Malekkhetabi: The use of undifferentiated bone marrow stromal cells for sciatic nerve regeneration in rats. Int. J. Oral Maxillofac. Surg. 2012; 41: 650–656. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. R. Mohammadi 1 , S. Azizi 1 , N. Delirezh 2 , R. Hobbenaghi 3 , K. Amini 4 , P. Malekkhetabi 2 1 Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran; 2 Department of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia University, Urmia, Iran; 3 Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran; 4 Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada Abstract. In recent years, cell transplantation has become a focus of attention and reliable outcomes have been achieved in regeneration of the sciatic nerve. The effect of undifferentiated bone marrow stromal cells (BMSCs) on peripheral nerve regeneration was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using an inside-out vein graft (IOVG) filled with undifferentiated BMSCs (2  10 7 cells/ml). In the control group, the vein was filled with phosphate buffer saline alone. The regenerated fibres were studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was based on functional (walking track analysis), histomorphometric and immuohistochemical (Schwann cell detection by S100 expression) criteria. The functional study confirmed significant recovery of regenerated axons in the IOVG/BMSC group (P < 0.05). Quantitative morphometric analyses of regenerated fibres showed the number and diameter of myelinated fibres in the IOVG/BMSC group were significantly higher than in the control group (P < 0.05). This demonstrates the potential for using undifferentiated BMSCs in peripheral nerve regeneration without the limitations of donor-site morbidity associated with isolation of Schwann cells. It also reduces costs because the interval between tissue collection and cell injection is reduced and the laboratory procedures are simpler compared to undifferentiated BMSCs. Key words: undifferentiated BMSCs; sciatic nerve repair, vein graft; bone marrow stromal cells. Accepted for publication 27 October 2011 Available online 7 December 2011 In spite of the presence of various nerve coaptation materials and techniques, achievement of desired functional periph- eral nerve regeneration is still inadequate 3 . Traumatic nerve injury resulting in periph- eral nerve gap often requires a graft to bridge the defect. Autologous nerve graft- ing is the method of choice for bridging peripheral nerve gaps, but it has the dis- advantage of sacrificing a functional nerve. Numerous surgical techniques are per- formed each year for peripheral nerve regeneration 12 . Vein has been used experi- mentally as a conduit; it has the advantages of no donor morbidity, ease of harvesting and transplanting, availability, affordabil- ity and no foreign body reactions 2,26 . In the last few years, cell transplantation has become the focus of attention, espe- cially that of Schwann cells, and reliable outcomes have been achieved in the regeneration of the sciatic nerve. It has been shown that transplantation of differ- entiated bone marrow stromal cells (BMSCs) into silicone tube, vein graft and cut ends of nerves exerts a beneficial effect on peripheral nerve regenera- tion 6,7,9,11 . To the authors’ knowledge, there is no report of the transplantation of undifferentiated BMSCs into an inside- out vein graft (IOVG) in the literature. The objective of present study is to elicit functional recovery in peripheral nerve injury over a 10-mm gap defect by undifferentiated fibroblast-like BMSC implantation into IOVG and to evaluate Int. J. Oral Maxillofac. Surg. 2012; 41: 650–656 doi:10.1016/j.ijom.2011.10.028, available online at http://www.sciencedirect.com 0901-5027/050650 + 07 $36.00/0 # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.