Stem cell therapy in spinal cord injury in vivo and postmortem tracking of bone marrow Mononuclear or mesenchymal stem cells

The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally. The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells. All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP(+)Luc(+) neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48-64 % and 68-72 %; 44-80 %; 8 and 18 within Groups III and IV respectively. MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.This study was supported by grants from the Turkish Scientific Research Council TUBITAK, Ankara University Research Resources (SBAG) and the Turkish Academy of Sciences