Intravenous administration of DPSCs and BDNF improves neurological performance in rats with focal cerebral ischemia

Zhang,Xuemei; Zhou,Yinglian; Li,Hulun; Wang,Rui; Yang,Dan; Li,Bing; Fu,Jin

doi:10.3892/ijmm.2018.3517

Intravenous administration of DPSCs and BDNF improves neurological performance in rats with focal cerebral ischemia

Authors:
- Xuemei Zhang
- Yinglian Zhou
- Hulun Li
- Rui Wang
- Dan Yang
- Bing Li
- Jin Fu
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Affiliations: Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: February 28, 2018 https://doi.org/10.3892/ijmm.2018.3517
Pages: 3185-3194
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dental pulp stem cells (DPSCs) are considered as an ideal stem cell source for the treatment of neurological diseases. In this study, we evaluated the therapeutic potency of DPSCs and brain-derived neurotrophic factor (BDNF) in focal cerebral ischemia using animal models. Following middle cerebral artery occlusion (MCAO), rats were randomized into four groups: the BDNF, DPSCs, DPSCs+BDNF and the controls injected with saline. DPSCs were transplanted and BDNF was injected into the DPSCs+BDNF group via the tail vein. The fate of the transplanted DPSCs in rat brains was evaluated using immunofluorescence, immunohistochemistry, western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Adhesive removal tests and the modified neurological severity scores were used to estimate the restoration of neurological function. Proliferation of intravenously transplanted DPSCs was observed in the peripheral ischemic regions of the MCAO models. A green fluorescent dye PKH67 was used to label cells. PKH67-labeled DPSCs were co-localized with neuronal cell markers and 4',6-diamidino‑2-phenylindole (DAPI). DPSC transplantation combined with BDNF induced the expression of neural differentiation markers such as nestin, doublecortin (DCX) and neuronal specific filament (NF-H), suggesting that BDNF enhances the survival of DPSCs and differentiation into neuronal cells. Treatment with DPSCs combined with BDNF promoted the recovery of neurological function more effectively compared with BDNF injection or DPSC transplantation alone. In conclusion, treatment with DPSCs combined with BDNF enhances neurological recovery after stroke suggesting a novel therapeutic strategy against cerebral ischemia.

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