I031 Analyzing cell surface markers, donor age, and passage number of bone marrow-derived mesenchymal stem cells in the treatment of motor deficits in the R6/2 mouse model of Huntington’s disease

<h3>Background</h3> Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in Huntingtin gene (HTT). Previous pre-clinical studies have shown the treatment effects of mesenchymal stem cells (MSCs) in HD. However, we showed that the therapeutic effect of MSCs for HD depends on cell culture passage number, with higher passage MSCs (P40 to P50) showing delayed onset of HD symptoms, most likely through the release of neurotrophic factors. Objective: The present study examined two crucial aspects – (1) the donor age and (2) the passage number of the bone marrow derived MSCs (BM-MSCs) in alleviating motor deficits in R6/2 HD mice. <h3>Methods</h3> BM-MSCs obtained from 5-week, 6-months, and 10-months-old healthy mice at different passage numbers, which were intrastriatally transplanted into the R6/2 HD mice. Animals underwent behavioral testing to assess HD symptoms following treatment. Further, the BM-MSCs were sorted using FACS for different surface-markers to identify a sub-population of MSCs with maximum therapeutic effects for HD. <h3>Results</h3> Our findings indicated that higher passaged MSCs, which were derived from a younger donor, alleviated motor deficits in R6/2 HD mice. Further, BM-MSCs that were CD90+ alone and CD105+ alone showed reduced survival rates and increased morphological changes over time in culture when compared to the BM-MSCs containing mixed populations. Moreover, the sub-population of MSCs expressing Sca1+ were predominant in culture at all passages. <h3>Conclusions</h3> Identifying a specific sub-population of MSCs with particular surface markers, age-donor, and passage numbers are important factors when designing MSCs-based therapies for HD. <h3>Funding</h3> Support for this study was provided by the Neuroscience program, the College of Medicine, the E. Malcolm Field and Gary Leo Dunbar Endowed Chair of Neuroscience and the John G. Kulhavi Professorship in Neuroscience at CMU.