Human Umbilical Cord Matrix Stem Cells Reverse Oxidative Stress-Induced Cell Death and Ameliorate Motor Function and Striatal Atrophy in Rat Model of Huntington Disease

Abstract

Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD. To this end, UCMSCs were isolated, immunophenotypically characterized by the positive expression of MSC markers, and exhibited multilineage potentiality. Besides, synthesis of neurotrophic factors of GDNF and VEGF by UCMSC was confirmed. Initially, PC12 cells were exposed to superoxide in the presence of conditioned media (CM) collected from UCMSC (UCMSC-CM) and cell viability plus neuritogenesis were measured. Next, bilateral striatal transplantation of UCMSC in 3-nitropropionic acid (3-NP) lesioned rat models was conducted, and 1 month later, post-graft analysis was performed. According to our in vitro results, CM of UCMSC protected PC12 cells against oxidative stress and considerably enhanced cell viability and neurite outgrowth. On the other hand, transplanted UCMSC survived, decreased gliosis, and ameliorated motor coordination and muscle activity, along with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. Collectively, our findings imply that UCMSCs provide an enriched platform by largely their paracrine factors, which downgrades the unfavorable effects of oxidative stress.

Keywords: Cell therapy; Huntington disease; Mesenchymal stem cells; Umbilical cord.