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.
Subject(s)
Acetals/chemistry , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Curcumin/therapeutic use , Delayed-Action Preparations/chemistry , Polymers/chemistry , Spinal Cord Injuries/therapy , Spinal Cord/drug effects , Stem Cell Transplantation , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cells, Cultured , Curcumin/administration & dosage , Curcumin/chemistry , Female , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/chemistry , Neuroprotective Agents/therapeutic use , Rats, Sprague-Dawley , Recovery of Function , Spinal Cord/physiopathology , Spinal Cord Injuries/physiopathology , Stem Cell Transplantation/methodsABSTRACT
Animal experimentation models are a necessary prerequisite to human trials for the use of regenerative medicine in the treatment of spinal cord injuries. Considerable effort is required for the generation of a consistent and reproducible methodology to incur an injury and evaluate the results. The traumatic contusion model has been accepted as a model that closely mimics a typical human traumatic injury, and here we detail step by step an approach to generate a reproducible lesion in rats. Acute cell transplantation by intramedullar or intrathecal administration is described for regenerative interventions. The same model is suitable to design subacute or chronic therapeutic approaches by interventions 1 week or 1 month after lesion.