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

• Published in: Biomaterials Vol. 113; pp. 18 - 30
• Main Authors: Requejo-Aguilar, Raquel, Alastrue-Agudo, Ana, Cases-Villar, Marta, López-Moncholi, Eric, England, Richard, Vicent, María J, Moreno-Manzano, Victoria
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2017
• Subjects: Acetals - chemistry; Advanced Basic Science; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Bioavailability; Cells, Cultured; Conjugates; Curcumin; Curcumin - administration & dosage; Curcumin - chemistry; Curcumin - therapeutic use; Delayed-Action Preparations - chemistry; Dentistry; Ependymal progenitor stem cells; Female; Injuries; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - chemistry; Neuroprotective Agents - therapeutic use; Polymer Therapeutics; Polymers - chemistry; Rats, Sprague-Dawley; Recovery; Recovery of Function; Rho kinase; Spinal cord; Spinal Cord - drug effects; Spinal Cord - physiopathology; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Spinal cord injury; Stem Cell Transplantation - methods; Strategy; Surgical implants; Therapy; Ependymal progenitor stem cells; Curcumin; Rho kinase; Spinal cord injury; Polymer therapeutics; Polymer Therapeutics
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2016.10.032

Abstract 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.