Proteomic analysis of ischemic rat brain after human mesenchymal stem cell transplantation

Abstract

An emerging paradigm in the treatment of stroke in patients with fixed neurologic deficits is stem cell therapy. Mesenchymal stem cells (MSCs) are attractive candidate cells for transplantation because they enhance endogenous repair systems, and the process is highly feasible. In order to further understand the complexity of the biochemical and physiological changes that occur after treatment with human MSCs (hMSC) in a rat model of stroke, we performed proteomic analysis of three groups: sham group, transient middle cerebral artery occlusion (tMCAo) group, and hMSC treated tMCAo group. Using 2-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we identified 14 proteins with altered expression patterns among the treatment groups. Differential protein expression was confirmed by western blotting. Two proteins that were upregulated in both the tMCAo group and the hMSC treated tMCAo group relative to sham were annexin A3 and GRP78, proteins involved in angiogenesis and neuroprotection. Two proteins that were elevated in the tMCAo group relative to the sham group and recovered to normal levels in the hMSC treated tMCAo group were synaptosomal-associated protein-25 (SNAP-25) and transitional endoplasmic reticulum ATPase, proteins involved in neuron loss and apoptosis. Our results revealed differential proteomic profiles that characterize the brain of the hMSC transplanted MCAo rat. These proteomic profiles contribute to the understanding of the mechanisms underlying the efficacy of MSC in stroke therapy.