Systematic Comparison Suggesting Intranasal Administration was the Best Clinical Practice among the Three Transplantation Ways of Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) in Hypoxic-ischaemic brain damage (HIBD) Rat Model

Abstract

Abstract Aims Hypoxic-ischaemic brain damage (HIBD) remains a common sequelae of various nervous system diseases. Human umbilical cord derived mesenchymal stem cells (hUC-MSCs) transplantation was considered to be promising in treating HIBD. However, it remains open the best administration way to transplant hUC-MSCs. In this study, we systematically compared the three administration ways —— the intravenous, the intracerebral and the intranasal administration for the first time to guide the best clinical practice. Methods The HIBD rat models were built on postnatal day 7(PN7). And rats were divided into five groups: sham, HIBD, HIBD + IV (intravenous administration), HIBD + IN (intranasal administration) and HIBD + IC (intracerebral administration). The behavioral experiments were used to compare the motor function、learning and memory function improvement of three administration ways, where the motor function of rats on PN10 and PN21 were evaluated by hanging wire and vertical pole test, and the learning and memory function of rats were evaluated by the Morris water maze (MWM) test. Moreover, the pathological tests were used to compare the pathological repair effects of three administration ways: the morphological changes of brain tissue were tested by Haematoxylin and eosin staining; the proliferation of reactive astrocytes were compared by detecting the expression of glial fibrillar acidic protein (GFAP), and the number of neuronal apoptosis in cortex and hippocampus were compared by TUNEL staining. Results The motor function of rats in HIBD group was significantly lower than that in sham group on the PN10, both in hanging wire and vertical pole tests (P < 0.0001). This shows the effectiveness of our HIBD model. According to the hanging wire test, the improvement of motor function in HIBD + IN group and HIBD + IC group were more obvious than that HIBD + IV group (P < 0.05), but no significant difference between HIBD + IN group and HIBD + IC group(P > 0.05).