The optimal dose of human umbilical-cord mesenchymal stem cells (hUC-MSCs) on hypoxic ischemic brain damage(HIBD) rats via intranasal transplantation

Abstract

Background: Hypoxic ischemic brain damage(HIBD) cause permanent damage to the central nervous system (CNS), including mental retardation, aphasia, epilepsy, cerebral palsy, and developmental delays. Recently, human umbilical cord mesenchymal stem cells (hUC-MSCs) have emerged as a promising cell therapy in HIBD. The optimal dose of stem cell therapy remains open. Methods: Previously, we conducted a study to identify that the best route of administration of hUC-MSCs to HIBD rat model is intranasal transplantation. In this study, we conducted the comparison experiments for the optimal dose of MSC via the best route of administration, intranasal transplantation. Four different doses (0.5*106, 1.0*106, 1.5*106, 2.0*106) of hUC-MSCs were injected to HIBD rats (obtained HIBD at 7th day after birth) on the10th day after birth. The body weight, hanging wire test and Morris Water Maze test were used on the 28th day of different groups of rats to compare their motor function, memory, and learning ability. The HE staining was used to compare the morphological differences of brain tissues of rats in different groups. Moreover, the immunohistochemistry was adopted to compare the morphology and number of astrocytes and microglia in cortex and CA1, CA3 region of the brain of different groups. Results: All the four different doses of hUC-MSCs treatment significantly improved their body weight, the motor function, memory, learning ability, the morphology and number of astrocytes and microglia in cortex and CA1, CA3 region of HIBD rats. The 1.5*106 of hUC-MSCs group significantly outperform other three groups (0.5*106, 1.0*106, 2.0*106) on both neurobehavioral motor function improvement and morphological improvement, i.e., reducing the number of astrocytes and microglia in cortex and CA1, CA3 region of HIBD rats. The study suggests that 1.5*106 of hUC-MSCs was the optimal dose for rats who obtained HIBD at 7th day after birth and injected by intranasal transplantation on the 10th day after birth.