Chinese Journal of Tissue Engineering Research ›› 2010, Vol. 14 ›› Issue (27): 5028-5032.doi: 10.3969/j.issn.1673-8225.2010.27.020

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Intravenous transplantation of glial cell-derived neurotrophic factor gene modified CD34+ cells for treating cerebral infarction in spontaneous hypertensive rats

Ou Ya-li, Yu Guo-long, Yang Tian-lun, Fang Li, Hu Ke   

  1. Department of Cardiology, Xiangya Hospital, Central South University, Changsha  410008, Hunan Province, China
  • Online:2010-07-02 Published:2010-07-02
  • Contact: Yu Guo-long, Professor, Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China yuguolong123@ yahoo.com.cn
  • About author:Ou Ya-li☆, Doctor, Physician, Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China ou-yali@hotmail.com
  • Supported by:

    the National Natural Science Foundation of China, No. 30572079*

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Abstract:

BACKGROUND: Previous studies have confirmed that direct administration of glial cell-derived neurotrophic factor (GDNF) or viral vector carrying GDNF gene can significantly reduce cerebral infarction volume, promote outcomes of the recovery of nerve function, but the therapeutic method is invasive and limits in clinic.
OBJECTIVE: To observe the outcomes of intravenous transplantation of human umbilical cord blood (hUCB) CD34+ cells transfected with GDNF gene in spontaneous hypertensive rats with cerebral infarction and to explore its mechanism.
METHODS: CD34+ cells isolated from hUCB were transfected by the pEGFP-GDNF plasmid and pEGFP blank vector to prepare pEGFP-GDNF-CD34+ and pEGFP-CD34+ cells. Sixty adult male spontaneous hypertensive rats with middle cerebral artery occlusion (MCAO) were randomly divided into three groups: pEGFP-GDNF-CD34+ cell group, pEGFP-CD34+ cell group and saline group. Neurological functional measurements were performed using the modified neurological severity score. Quantitative histological determinations of infarct volume were performed using standard TTC staining and quantitative image analysis. The GDNF level in the cell culture or the cerebral tissue was measured by enzyme linked immunosorbent assay. The survival and migration of green fluorescent protein (GFP)-labeled CD34+ cells and the expression of astrocytic marker-glial fibriliary acidic protein (GFAP) and the neuron marker-neuronal nuclei (NeuN) were detected by immunohistochemical and fluorescent staining.
RESULTS AND CONCLUSION: Intravenous transplantation of pEGFP-GDNF-CD34+ cells migrated into ischemic-injured cerebral hemisphere, survived and differentiated into neural cells in ischemic region of spontaneous hypertensive rats, and promoted the recovery of nerve function. GDNF gene-transfected CD34+ cells survived in the brain tissue and differentiated into neural cells, and its neurological protection effect was superior to CD34+ cells. The increased GDNF level in cerebral tissue was one of possible mechanisms responsible for focal cerebral ischemia in spontaneous hypertensive rats after transplantation of between GDNF gene modified CD34+ cells and CD34+ cells.

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