Nanoparticle technologies offer a non-invasive means to deliver basic fibroblast growth factor (bFGF) for the treatment of spinal cord injury (SCI). However, the inability of bFGF to accumulate at the injury site and inefficient penetration across the blood-spinal cord barrier (BSCB) remain challenges. The present study describes a dual-targeting liposome (bFGF@Lip-Cp&Rp) with injury lesion targeting and BSCB-penetrating capability to deliver bFGF for SCI treatment. The CAQK peptide (Cp) with injury lesion targeting ability and R2KC peptide (Rp) with BSCB-penetrating capability were grafted onto the liposomes for a flexible and non-invasive drug delivery systems preparation. Results exhibit that the dual-targeted liposomes could significantly cross the BSCB and accumulate at the injury site. During the early stage of SCI, bFGF@Lip-Cp&Rp promotes repair of BSCB and facilitates M2-polarization of macrophages. Regular delivery of bFGF@Lip-Cp&Rp increase HUVECs tube formation and angiogenesis, ameliorate the microenvironment of lesion site, suppress the neuronal apoptosis and axonal atrophy in SCI rats. Importantly, continuous treatment of bFGF@Lip-Cp&Rp supports the restoration of limb motor function in SCI rats. In summary, this research implies that the injury site-targeting and BSCB-penetrating liposomes could be a promising therapeutic approach for the treatment of SCI.

In the acute phase of spinal cord injury, the initial injury triggers secondary damage due to neuroinflammation, leading to the formation of cavities and glial scars that impair nerve regeneration. Following injuries to the central nervous system, early mobilization promotes the recovery of physical function. Therefore, in the present study, we investigated the effects of early mobilization on motor function recovery and neuroinflammation in rats. Early mobilization of rats with complete spinal cord transection resulted in good recovery of hindlimb motor function after 3 weeks. At 1 week after spinal cord injury, the early-mobilized rats expressed fewer inflammatory M1 microglia/macrophages and more anti-inflammatory M2 microglia. In addition, significantly more matrix metalloproteinase 2 (MMP2)-positive cells were observed at the lesion site 1 week after injury in the early-mobilized rats. Multiple labeling studies suggested that many MMP2-positive cells were M2 microglia. MMP9-positive cells that highly co-expressed GFAP were also observed more frequently in the early-mobilized rats. The density of growth-associated protein-positive structures in the lesion center was significantly higher in the early-mobilized rats at 3 weeks after spinal cord injury. The present results suggest that early mobilization after spinal cord injury reduced the production of M1 microglia/macrophages while increasing the production of M2 microglia at the lesion site. Early mobilization might also activate the expression of MMP2 in M2 microglia and MMP9 in astrocytes. These cellular dynamics might suppress neuroinflammation at the lesion site, thereby inhibiting the progression of tissue destruction and promoting nerve regeneration to recover motor function.

For the past few decades, spinal cord injury (SCI) has been believed to be an incurable traumatic condition, but with recent developments in stem cell biology, the field of regenerative medicine has gained hopeful momentum in the development of a treatment for this challenging pathology. Among the treatment candidates, transplantation of neural precursor cells has gained remarkable attention as a reasonable therapeutic intervention to replace the damaged central nervous system cells and promote functional recovery. Here, we highlight transplantation therapy techniques using induced pluripotent stem cells to treat SCI and review the recent research giving consideration to future clinical applications.

Bone morphogenetic protein-7 (BMP7), a member of the transforming growth factor-β (TGF-β) superfamily, has various effects in many biological events. However, there is little information on BMP7 expression in the adult central nervous system (CNS). Therefore, we investigated BMP7 levels in the adult rat CNS using immunohistochemistry. Abundant BMP7 expression was seen in astrocytes throughout the CNS and strong BMP7 expression was also observed in neuropils of the gray matter. Furthermore, BMP7 expression was observed in several kinds of neurons, including oxytocin, dopaminergic and noradrenergic neurons. These data suggest that BMP7 is widely expressed throughout the adult CNS, and support the idea that BMP7 plays pivotal roles in the adult brain, as well as in the developing brain.