Effects of magnetic nanoparticle-incorporated human bone marrow–derived mesenchymal stem cells exposed to pulsed electromagnetic fields on injured rat spinal cord Hyunjin Cho 1 Yun-Kyong Choi 2 Dong Heon Lee 3 Hee Jung Park 2 Young-Kwon Seo 1,2 Hyun Jung 3,4 Soo-Chan Kim 5 Sung-Min Kim 2 Jung-Keug Park 1,2* 1 Research Institute of Biotechnology, Dongguk University, Seoul, Korea 2 Department of Medical Biotechnology, Dongguk University, Seoul, Korea 3 Advanced Functional Nanohybrid Material Lab, Department of Chemistry, Dongguk University, Seoul, Korea 4 Department of Energy and Materials Engineering, Dongguk University, Seoul, Korea 5 Graduate School of Bio & Information Technology, Hankyong National University, Anseong-si, Kyonggi-do, Korea Abstract Transplanting mesenchymal stem cells into injured lesions is currently under study as a therapeutic approach for spinal cord injury. In this study, the effects of a pulsed electromagnetic field (PEMF) on injured rat spinal cord were investigated in magnetic nanoparticle (MNP)-incorporated human bone marrow–derived mesenchymal stem cells (hBM-MSCs). A histological analysis revealed significant differences in MNP-incorporated cell distribution near the injured site under the PEMF in comparison with that in the control group. We confirmed that MNP-incorporated cells were widely distributed in the lesions under PEMF. The results suggest that MNP-incorporated hBM-MSCs were guided by the PEMF near the injured site, and that PEMF exposure for 8 H per day over 4 weeks promoted behavioral recovery in spinal cord injured rats. The results show that rats with MNP-incorporated hBM-MSCs under a PEMF were more effective on the Basso, Beattie, and Bresnahan behavioral test and suggest that the PEMF enhanced the action of transplanted cells for recovery of the injured lesion. C  2013 International Union of Biochemistry and Molecular Biology, Inc. Volume 60, Number 6, Pages 596–602, 2013 Keywords: human bone marrow–derived mesenchymal stem cells, pulsed electromagnetic field, magnetic nanoparticle, spinal cord injury 1. Introduction Spinal cord injury (SCI) is damage to the spinal cord that results in loss of function such as mobility or feeling. SCI affects many people, resulting in local and distant damage to the Abbreviations: PEMF, pulsed electromagnetic field; MNP, magnetic nanoparticle; SCI, spinal cord injury; PEG, polyethylene glycol. ∗ Address for correspondence: Jung-Keug Park, PhD, Research Institute of Biotechnology, Department of Medical Biotechnology, Dongguk University, Seoul 100–715, Korea. Tel.: +82 2 22608535; Fax: +82 2 22713489; e-mail: jkpark@dongguk.edu. Received 30 November 2012; accepted 13 February 2013 DOI: 10.1002/bab.1109 Published online 26 August 2013 in Wiley Online Library (wileyonlinelibrary.com) cord followed by a range of cellular disturbances, hemostatic imbalance, and ionic and neurotransmitter derangements [1]. The targets for improving function post-SCI are directed toward limiting secondary injury involving free radical production [2], inlammation [3], apoptosis of neurons [4], and activation of the glial population [5]. Stem cells are a promising therapy for tissue regenera- tion [6]. Embryonic stem cells (ESCs) were irst used in SCI by McDonald et al. in 1999 [7]. That study reported that appropriate differentiation of ESCs was associated with im- proved functional recovery. Another report demonstrated that neural stem cells can be used in combination with im- munosuppression and growth factors to treat SCI [8]. Bone marrow–derived mesenchymal stem cells (BM-MSCs) are easily obtained from adult BM and can be expanded ex vivo [9]. Many studies have reported on differentiating BM-MSCs into 596