HipOP mesenchymal population has high potential for repairing injured peripheral nerves.

ABSTRACT

Bone marrow stromal cells (BMSCs) are reportedly a heterogeneous population of mesenchymal stem cells (MSCs). Recently, we developed a simple strategy for the enrichment of MSCs with the capacity to differentiate into osteoblasts, chondrocytes, and adipocytes. On transplantation, the progenitor-enriched fractions can regenerate the bone with multiple lineages of donor origin and are thus called "highly purified osteoprogenitors" (HipOPs). Although our previous studies have demonstrated that HipOPs are enriched with MSCs and exhibit a higher potential to differentiate into osteoblasts, adipocytes, and chondrocytes than BMSCs, their potential to differentiate into neural cells has not been clarified. In this study, we evaluated the efficacy of HipOPs as a resource of neural stem cells. The neurosphere assay showed that neurospheres formed by HipOPs exhibited self-renewal ability and their size was generally larger than that of neurospheres formed by BMSCs. A limiting dilution assay was used to evaluate the frequency of neural progenitors in BMSCs and HipOPs. The results demonstrated that the frequency of neural progenitors in HipOPs was 120-fold higher than that in BMSCs. Furthermore, to investigate the in vivo regenerative potential of the peripheral nerve, we modified a murine peripheral nerve injury experimental model and demonstrated that HipOPs exhibit a higher efficacy in repairing injured peripheral nerves. These findings suggest that HipOPs are a useful cell resource for regenerative therapies such as that in case of peripheral nerve injury.