Thus, the Schwann-spheres enhanced myelin formation and neurite outgrowth compared with the effects of mature Schwann cells in vitro. This is the first report that Schwann-cell precursors/immature Schwann cells, in the form of cultured ����Schwann-spheres,���� can be isolated from adult peripheral nerves. Mature myelinating and non-myelinating cells respond to nerve injury by reverting to a molecular phenotype similar to that of immature Schwann cells, to provide essential support for axonal regrowth. Therefore, we hypothesized that undifferentiated spheres could be obtained from adult injured peripheral nerves. Indeed, here we demonstrated that adult peripheral nerves harvested at specific time points after contusive injury could generate de-differentiated spheres under the floating culture condition with EGF, FGF and fetal bovine serum. These Schwann-spheres, which exhibited a high selfrenewal capacity, consisted of Schwann-cell precursors/immature Schwann cells. Immunocytochemistry and Cre/lox system-mediated lineage tracing analyses showed that the Schwann-spheres BIO originated from myelinating mature Schwann cells, which dedifferentiated after peripheral nerve injury. In addition, immunohistochemical and RT-PCR analyses revealed that the Schwannspheres could differentiate into the Schwann-cell lineage, suggesting that mature Schwann cells de-differentiate into Schwann-cell precursors/immature Schwann cells, but not into neural-crest stem cells, unlike the spheres derived from fetal sciatic nerves or DRGs. Schwann cells are considered a promising candidate for cellular transplantation therapies to repair the injured central or peripheral nervous system. Previous studies have shown that Schwann cells promote axonal growth, mainly from sensory and proprioAlprazolam spinal neurons. Moreover, Schwann cells myelinate the ingrowing axons and re-establish axonal conduction. Although Schwann-cell transplants have shown only limited results, in that few long-tract axons enter and few axons exit the grafts, a combination therapy of Schwann cells with neuroprotective agents, molecules that modify the glial scar, neurotrophic factors, or camp, enhances the ingrowth of long-descending axons and the exit of fibers, thereby improving functional recovery. There is a strong current interest in Schwann-cell-based transplantation strategies for the treatment of spinal cord injuries.