Transplantation of differentiated bone marrow stromal cells promotes motor functional recovery in rats with stroke

Abstract

Objective: To investigate the effects of transplantation into rats with stroke of bone marrow-derived mesenchymal stem cells (MSCs) induced by brain-derived neurotrophic factor (BDNF).

Materials and methods: MSCs were harvested from 6-week-old Sprague–Dawley male rats, and transplanted into adult Sprague–Dawley male rats with transient middle cerebral artery occlusion. At 48 hours after stroke, the adult rats, weighing 250–280 g, were injected via the tail vein with 1×10⁷ MSCs or MSCs induced by BDNF (BDNF-MSCs) suspended in 1 ml phosphate-buffered saline. All animals underwent the neurological function test for 14 days. Infarct volume and blood–brain barrier permeability assay were assessed on day 14 post-middle cerebral artery occlusion. Western blotting and immunohistochemical staining were used to detect the protein expression of neuron-specific enolase (NSE).

Results: Both BDNF-MSCs and MSCs produced improvement in neurological deficits compared with vehicle controls on day 14 (P<0·05). In particular, the group transplanted with BDNF-MSCs exhibited significant recovery of motor function compared with the group transplanted with MSCs alone (P<0·05). Both BDNF-MSCs and MSCs, but particularly the former, reduced infarct volume, improved blood–brain barrier dysfunction, reduced serum NSE levels, activated the NSE activity, and inhibited neuronal apoptosis in the ischemic boundary zone.

Conclusions: BDNF-MSCs might contribute to the motor function improvement partly by reducing neuronal damage via upregulating the NSE expression level and inhibiting neuronal apoptosis.

Keywords:

• Bone marrow stromal cells
• Brain-derived neurotrophic factor
• Middle cerebral artery occlusion
• Transplantation

This work was supported by the key project of National/Guangdong Nature Science Foundation of China (U1032004); National Nature Science Foundation of China (30170510, 30870851, and 81160152); Guang Dong Nature Science Foundation (970061); and Guangxi Natural Science Foundation (0542053).