Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery

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• 作者：Raquel Requejo-Aguilar^a ; ¹ ; Ana Alastrue-Agudo^a ; ¹ ; Marta Cases-Villar^a ; Eric Lopez-Mocholi^a ; Richard England^b ; Marí ; a J. Vicent^b ; ^{mjvicent@cipf.es" class="auth_mail" title="E-mail the corresponding author} ; Victoria Moreno-Manzano^a ; ^c ; ^{vmorenom@cipf.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Curcumin ; Polymer Therapeutics ; Spinal cord injury ; Ependymal progenitor stem cells ; Rho kinase
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：113
• 期：Complete
• 页码：18-30
• 全文大小：3550 K

文摘

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans.