LETTER TO THE EDITOR Ferulic acid pretreatment could improve prognosis of autologous mesenchymal stromal cell transplantation for diabetic neuropathy SOLMAZ MIRZAMOHAMMADI 1 , MOHAMMAD HADI NEMATOLLAHI 2 , MEHRZAD MEHRBANI 3,4 & MEHRNAZ MEHRABANI 5 1 School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran, 2 Research Center for Hydatid Disease in Iran, Department of Biochemistry, Kerman University of Medical Sciences, Kerman, Iran, 3 Herbal andTraditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran, 4 Department of Traditional Medicine, School of Traditional Medicine, Kerman University of Medical Sciences, Kerman, Iran, and 5 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran To the Editor: Neuropathy is one of the most common complica- tions of both type 1 and type 2 diabetes. Patients with diabetic neuropathy (DN) present with patho- logical features, including impaired vascularity and deficiency of angiogenic and neurotropic factors in nerves. Among various etiologies described for DN, hyperglycemia obviously plays an important role in the onset and progression of disease. Therefore, tight glycemic control and targeting glucose metabol- ic pathways by specific agents seem to be useful therapeutic strategies for halting the progression of DN. However, clinically, these therapeutic ap- proaches did not show desirable therapeutic efficacy in the established neuronal damage. It underscores the need for requirement of more efficient strategies at the advanced stage of DN, including those activating angiogenic and neurotrophic pathways. Recently, cell therapy based on stem cells has been suggested as an attractive strategy for the treatment of DN [1]. Mesenchymal stromal cells (MSCs) are multipotent cells, capable of moving toward sites of injury, releas- ing various neurotrophic and angiogenic factors and differentiating into multi-lineage cell types, particu- larly neuron-like cells. These features make MSCs a suitable candidate for cell-based therapeutic strate- gies in DN [2]. Autologous MSCs, because they are not subject to immune rejection in contrast to allo- geneic MSCs, have been considered an excellent choice for curative angiogenic and neurotrophic therapies [3]. However, oxidative stress as a consequence of high blood glucose causes serious damage to vital media- tors in autologous MSCs. Our recent report demonstrated that diabetic MSCs show reduced pro- liferation rate and impaired paracrine effects including secretion of angiogenic factors [4]. This highlighted that the use of autologous diabetic MSCs as a source for treating diabetic complications may still be con- troversial. HIF-1 is illustrated as one of the impaired vital mediators [4]. HIF-1, a transcription complex, consists of HIF-1α that contains an oxygen-dependent degra- dation domain, and HIF-1β. HIF-1α plays a central role in the cellular responses to changes in oxygen availability. Under low-oxygen conditions, HIF-1α degradation via the ubiquitin-proteasome pathway is inhibited. It leads to HIF-1α aggregation in the nucleus and its binding to hypoxia-response ele- ments in the promoters of target genes. HIF-1α regulates the expression of potent angiogenic and neurotrophic factors including vascular endothelial growth factor, platelet-derived growth factor and others [5]. However, protein stability and also transactivation of HIF-1α protein are hampered under oxidative stress. In a high-glucose context, methylglyoxal level increased as a result of oxidative stress and prevented binding of HIF-1α to its Correspondence: Mehrnaz Mehrabani, PhD, Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. E-mail: mehrnaz.mehrabani@yahoo.com (Received 15 April 2016; accepted 15 April 2016) ISSN 1465-3249 Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcyt.2016.04.006 Cytotherapy, 2016; 18: 925–927