OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) on repairing brachial plexus injury in rabbits and their influence on expression of the extracellular signal-regulated kinase (ERK) pathway.
MATERIALS AND METHODS: With big-ear rabbits as the objects, the BMSCs were first isolated, and the cluster of differentiation (CD)45- and CD90+ BMSCs were sorted out via flow cytometry. BMSCs were transfected with red fluorescent protein (RFP), and the transfection effect was detected. Then, the big-ear rabbits were subjected to brachial plexus root avulsion injury (BPAI) to establish injury Model group and sham-operation group (Sham group). Later, the BMSCs were transfected with RFP to construct RFP-BMSCs. The RFP-BMSCs (5×106, Treat group) and normal saline (Model group) were intraperitoneally injected, and the recovery rate of wet weight of the upper limb muscle was measured by weighing. The injured nerve tissues were embedded for hematoxylin and eosin (HE) staining and observation of pathological changes. The electrophysiological measurement of the compound muscle action potential (CMAP) on the injured side was conducted for the rabbits to be sacrificed immediately using an electromyogram instrument, and the CMAP amplitude and latency were applied to evaluate the recovery of upper limb muscle. Finally, the location of RFP-BMSCs in the nerve tissues was traced by a fluorescence microscope, and the protein expression levels of phosphorylated ERK (p-ERK) and phosphorylated mitogen-activated protein kinase (p-MAPK) in the injured nerve tissues were determined by means of Western blotting.
RESULTS: Persistently expressed red fluorescence was observed in CD45- and CD90+ BMSCs sorted via flow cytometry under the fluorescence microscope, indicating that the RFP-BMSCs were constructed successfully. Compared with Sham group, Model group had a remarkably decreased recovery rate of wet muscle weight (p<0.05), while Treat group exhibited a notably increased recovery rate of wet muscle weight in comparison with Model group. The CMAP amplitude was reduced markedly (p<0.05), while the CMAP latency was prolonged significantly (p<0.05) in Model group compared with those in Sham group. Moreover, Treat group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than Model group (p<0.05). It was discovered under the fluorescence microscope that RFP-BMSCs were visibly arranged on both sides of nerve fibers in Treat group. The expressions of p-MAPK and p-ERK were raised prominently in Model group in comparison with those in Sham group (p<0.05), and they were lowered apparently in Treat group compared with those in Model group (p<0.05).
CONCLUSIONS: BMSCs can repair the impaired brachial plexus neurons and restore their physiological functions, and the protective effect of the BMSCs on the neurons is associated with the mediated MAPK/ERK pathway.Free PDF Download
To cite this article
M.-G. Guo, D.-P. Li, L.-X. Wu, M. Li, B. Yang
Bone marrow mesenchymal stem cells repair brachial plexus injury in rabbits through ERK pathway
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 3