Spinal cord injury (SCI) is a devastating neurological disorder that leads to motor, sensory, or autonomic dysfunction, and is associated with high rates of mortality and complications including bladder infection, renal failure, cardiovascular disease, and respiratory dysfunctions. There are approximately 180,000 new cases of SCI worldwide per year caused by traffic accidents, sports injuries, and other traumatic events according to an epidemiologic study

Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic (HI) brain injury. However, the poor survival of implanted NPCs in the HI host environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that is induced in response to a variety of pathological processes including inflammation and immunity. On the other hand, TNF-α has protective effects on cell apoptosis and death and affects the differentiation, proliferation, and survival of neural stem/progenitor cells in the brain. The present study investigated whether TNF-α pretreatment on human NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-α before being used in vitro experiments or transplantation. TNF-α significantly increased expression of cIAP2, and the use of short hairpin RNA-mediated knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced cytotoxicity. In addition, pretreatment of hNPCs with TNF-α mediated neuroprotection by altering microglia polarization via increased expression of CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, transplantation of TNF-α-treated hNPCs reduced infarct volume and improved neurological functions in comparison with non-pretreated hNPCs or vehicle. These findings show that TNF-α pretreatment, which protects hNPCs from HI-injured brain-induced apoptosis and increases neuroprotection, is a simple and safe approach to improve the survival of transplanted hNPCs and the therapeutic efficacy of hNPCs in HI brain injury.

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Front Cover: Biodegradable PLGA‐patterned substrates with immobilization of ECM proteins via a DOPA coating significantly promote contact guidance and neuronal differentiation of hNSCs. The addition of neurotrophic factor (NGF) further enhances neurogenesis of hNSCs, indicating a synergistic effect of biophysical and biochemical cues on hNSC differentiation. (Cover designed by J. Kim and K. Yang) Further details can be found in the article by K. Yang, E. Park, J. S. Lee, I.‐S. Kim, K. Hong, K. I. Park, S.‐W. Cho, H. S. Yang http://doi.wiley.com/10.1002/mabi.201500080.