ORIGINAL COMMUNICATION Treatment of Spinal Cord Injury: A Review of Engineering Using Neural and Mesenchymal Stem Cells MARTIN M. MORTAZAVI, 1 * OLIVIA A. HARMON, 2 NIMER ADEEB, 2 AMAN DEEP, 2 AND R. SHANE TUBBS 2,3,4 1 Department of Neurosurgery, University of Washington, Seattle, Washington 2 Pediatric Neurosurgery, Children’s of Alabama, Birmingham, Alabama 3 Department of Anatomical Sciences, St. George’s University, Grenada 4 Centre of Anatomy and Human Identification, University of Dundee, Dundee, United Kingdom Over time, various treatment modalities for spinal cord injury have been tri- aled, including pharmacological and nonpharmacological methods. Among these, replacement of the injured neural and paraneural tissues via cellular transplantation of neural and mesenchymal stem cells has been the most attractive. Extensive experimental studies have been done to identify the safety and effectiveness of this transplantation in animal and human models. Herein, we review the literature for studies conducted, with a focus on the human-related studies, recruitment, isolation, and transplantation, of these multipotent stem cells, and associated outcomes. Clin. Anat. 00:000–000, 2014. V C 2014 Wiley Periodicals, Inc. Key words: stem cell therapy; spinal cord injury; neural stem cells; mesenchy- mal stem cells; anatomy; nerve; trauma; disease; pathology; stem cells; paralysis; treatment INTRODUCTION Stem cells are nondifferentiating cells that have high proliferation, differentiation, and self-renewal potentials. The proliferation and self-renewal potential is achieved via the asymmetric division, in which one of the daughter cells becomes further differentiated, whereas the other maintains the characteristics of the cell of origin. In regard to their differentiation capacity, the stem cells can be divided into totipotent, pluripo- tent, multi- or oligo-potent, and unipotent stem cells. An example of totipotent stem cells is the fertilized egg, and they are capable of generating embryonal and extra-embryonal cells. With further specialization, pluripotent stem cells are formed, and they are capa- ble of differentiation into any cell of the three germ line (ectoderm, mesoderm, and endoderm). Good examples of these cells are the embryonic stem cells (ESC) and the induced pluripotent stem cells (iPSC). Multipotent stem cells are able to differentiate into dif- ferent types of cells within each germ line. An exam- ple of these is the neural progenitor/stem cell. It is evidenced that these cells are able to transdifferenti- ate into other germ lines’ cells. However, induced transdifferentiation may result in induced carcinogen- esis. Unipotent stem cells can differentiate into only one type of cells, and include neuroblast and glioblast, which give rise to neurons or glial cells, respectively (Nandoe Tewarie et al., 2009; Sahni and Kessler, 2010; Cherian et al., 2011). Both pluripotent and mul- tipotent cells may be used as a source of transplanted cells. For the purpose of cellular replacement, the more differentiated is the transplanted cell, the less risk of consequent teratoma. Thus, differentiation of the applied stem cells is required before transplanta- tion (Sahni and Kessler, 2010). *Correspondence to: Dr. Martin M. Mortazavi, Department of Neurosurgery, University of Washington, Seattle, Washington, USA. E-mail: mmortazavi@chsys.org Received 1 July 2014; Accepted 2 July 2014 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ca.22443 V V C 2014 Wiley Periodicals, Inc. Clinical Anatomy 00:00–00 (2014)