Repairing hypoxic-ischemic brain damage in neonatal rats by nasal transplantation of human umbilical cord mesenchymal stem cells

doi:10.3969/j.issn.2095-4344.1762

Abstract

Abstract:

BACKGROUND: Human umbilical cord mesenchymal stem cells exert significant neuroprotective effects in animals, including reducing neuronal apoptosis and promoting neuronal regeneration. Current approaches to transfer these cells include transvenous, arterial, lumbar puncture, brain stereotactic transplantation and lateral ventricle transplantation, but all of them are insufficient.
OBJECTIVE: To investigate the feasibility and effectiveness of nasal transplantation of human umbilical cord mesenchymal stem cells in the treatment of hypoxic-ischemic brain damage in neonatal rats.
METHODS: Ninety 7-day-old Sprague-Dawley rats (provided by the Experimental Animal Center of Shantou University Medical College) were randomly divided into three groups (n=30 per group): in sham operation group the left common carotid artery was only separated and then sutured; in model group, an animal model of hypoxic-ischemic brain damage was prepared through ligation and occlusion of the left common carotid artery combined with hypoxic chamber; in experimental group, the animal model was prepared as described in the model group, and then green fluorescent protein-labeled human umbilical cord mesenchymal stem cells were instilled into the nasal cavity of model rats. Brain tissue was taken 3 days after modeling, and Nissl staining, TUNEL detection, and immunofluorescence staining were performed. The memory and learning abilities of the rats were detected by water maze at 14 and 29 days after modeling. After 14-day water maze test, TUNEL staining of the brain tissue was performed. The animal experiment was approved by the Experimental Animal Ethics Committee of Shenzhen University Health Science Center with the approval No. 2016-121.
RESULTS AND CONCLUSION: (1) Nissl staining: Neurons in the cerebral cortex and hippocampal CA1 area of the model group were irregularly arranged, and there were few Nissl bodies. Compared with the model group, the neurons in the cerebral cortex and hippocampal CA1 area were arranged more regularly in the experimental group, and there were more Nissl bodies. (2) TUNEL staining: On 3 and 14 days after modeling, the number of apoptotic cells in the model group was significantly higher than that in the sham operation group (P < 0.05) and in the experimental group (P < 0.05). (3) Immunofluorescence staining: Green-labeled human umbilical cord mesenchymal stem cells were found in the brain tissue of the experimental group, mainly distributed in the hippocampus and cerebral cortex of the injured side. Green fluorescent protein-labeled cells were mainly visible in the injured hippocampus and cortex, but rarely detected in the non-injured brain tissues. Non-GFAP or NSE double staining cells were detected. (4) The average escape latency of the experimental group was lower than that of the model group (P < 0.05). Overall, these findings indicate that nasal transplantation of human umbilical cord mesenchymal stem cells can reduce neuronal apoptosis and improve memory and learning abilities of neonatal rats with hypoxic-ischemic brain damage.

Key words: stem cells, umbilical cord blood stem cells, mesenchymal stem cells, umbilical cord blood mesenchymal stem cells, transplantation, hypoxic-ischemic brain damage, intranasal delivery, water maze test

CLC Number:

Yang Hanhua, Tian Shufeng, Xie Lichun, Chen Yunbin, Ma Lian. Repairing hypoxic-ischemic brain damage in neonatal rats by nasal transplantation of human umbilical cord mesenchymal stem cells[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(21): 3386-3391.

Figures/Tables 1

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