Abstract
BackgroundSpinal cord injury (SCI) is one of the most severe central nervous system injuries. Currently, transplanting bone marrow mesenchymal stem cells (BMSCs) is considered a therapeutic option for SCI. Tanshinone IIA (TIIA) is one of the extracts obtained from Salvia miltiorrhiza Bunge, which has been shown to have some protective effects against SCI. The present research was aimed to explore whether TIIA would influence the fate of transplanted BMSCs in a rat model of SCI, especially with regard to their differentiation into neuronal cells.MethodsBone marrow mesenchymal stem cells were obtained from immature rats and identified using flow cytometry. After SCI, 1.0 × 107 cells labeled with PKH67 were transfused into the injured spinal cord. TIIA was first injected into the tail vein (30 mg/kg) 1 h before surgery. From day 1 to day 7 post-SCI, TIIA was injected (20 mg/kg) per day at the same time. Recovery of locomotor function and histological regeneration of the spinal cord were compared among the groups, with the differentiation and distribution of BMSCs determined anatomically and biochemically by the expression of neural cell markers.ResultsLocomotor assessments showed that the rats in the BMSCs + TIIA group exhibited higher scores (19.33 ± 0.58) than those in the other groups (13.67 ± 1.53, 17.67 ± 0.58, 18.00 ± 1.73). The area of the cavity in the BMSCs + TIIA rats was smaller than that in the other groups (1.30 ± 0.56, 10.39 ± 1.59, 6.84 ± 1.18, 4.36 ± 0.69). Co-expression of glial fibrillary acid protein was observed in transplanted BMSCs, with a reduced rate in the BMSCs + TIIA group relative to that in the SCI group. In contrast, the expression levels of Nestin, neuron-specific nuclear protein (NeuN) and neurofilament protein 200 (NF200) were greatest in the transplanted cells in the BMSCs + TIIA group.ConclusionsTanshinone IIA treatment enhances the therapeutic effects of BMSC transplant on SCI, likely by promoting the differentiation of neuronal cells.
Highlights
Spinal cord injury (SCI) is one of the most severe central nervous system injuries
There was no significant difference between the sham and bone marrow mesenchymal stem cells (BMSCs) + Tanshinone IIA (TIIA) groups, while there were significant differences among the other groups (i.e., SCI vs TIIA, SCI vs BMSCs, SCI vs BMSCs + TIIA, TIIA vs BMSCs, TIIA vs BMSCs + TIIA, BMSCs vs BMSCs + TIIA, ***P < 0.001; Fig. 1g)
The protein levels of glial fibrillary acid protein (GFAP) were significantly reduced in the BMSCs + TIIA group, while the protein levels of Nestin, neuron-specific nuclear protein (NeuN), and neurofilament protein 200 (NF200) were significantly higher, compared to those in the SCI group (n = 3, *P < 0.05, **P < 0.01, ***P < 0.001). These results indicated that combinational therapy with TIIA and BMSCs resulted in the production of a greater proportion of neuronal-like cells, and the combination therapy is a more effective treatment for SCI compared to monotherapy
Summary
Spinal cord injury (SCI) is one of the most severe central nervous system injuries. Among the potential drugs that may be helpful for SCI is Salvia miltiorrhiza Bunge (SMB), a traditional Chinese herb that is currently used for the treatment of various diseases, in particular cardiovascular and cerebrovascular cases [3, 4]. TIIA is the most abundant diterpene quinone, which has potential protective effects against atherosclerosis, cardiac hypertrophy, cardiac fibrosis, can attenuate oxidative stress induced apoptosis [6]. It recently has been used in treating cardiovascular diseases, hypertension and myocardial infarction [3]. It appears to have a protective effect against SCI by inhibiting proinflammatory processes and SCI-induced apoptosis [7, 8]
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