The distribution of transplanted human mesenchymal stem cells in the CNS of young Macaca fascicularis

• hMSCs was first transplanted into caudate nucleus of Macaca fascicularis directly.
• hMSCs have the ability of engraftment and migration throughout the host brain.
• hMSCs exhibit neural and glial phenotype upon incorporation into the host brain.
• Transplantation of hMSCs could upregulate the expression level of host N-cadherin.
• Human recombinant N-cadherin protein could induce migration of hMSCs in vitro.

Mesenchymal stem cell (MSC)-based therapies have generated much hope and promise as a potential source of cells for cell-based therapeutic strategies in pediatric degenerative diseases. However, the distribution and migratory routes of MSCs are unknown. Here, real-time PCR and microscopy were used to observe the migration and distribution of labeled human MSCs (hMSCs) transplanted into the striatum of young Macaca fascicularis. Moreover, the differentiation of hMSCs was also detected using immunofluorescence. We found that hMSCs were mainly located near the injection site in the brain and in the anterior brain after 2 weeks. After 4 weeks, the hMSCs had dispersed and could be detected in each brain slice and were more uniformly distributed than after 2 weeks. The hMSCs showed a preference for migration towards blood vessels, which may be one of the migratory routes used by hMSCs. Additionally, hMSCs could be observed to give rise to NeuN- and GFAP-positive cells. Transplanted hMSCs also increased the expression levels of N-cadherin in the host brain tissue, which may be one factor that drives the migration and differentiation of hMSCs after transplantation. These results provide preclinical evidence that MSC-based therapies may represent an efficacious alternative to more conventional treatment regimens for a variety of pediatric neurologic disorders.