Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.
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.
Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain.
Raquel
R
Requejo-Aguilar
Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain.
Ana
A
Alastrue-Agudo
Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain.
Marta
M
Cases-Villar
Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain.
Eric
E
Lopez-Mocholi
Polymer Therapeutics Laboratory, Príncipe Felipe Research Center, Valencia, Spain.
Richard
R
England
Polymer Therapeutics Laboratory, Príncipe Felipe Research Center, Valencia, Spain. Electronic address: mjvicent@cipf.es.
María J
MJ
Vicent
Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain; Universidad Católica de Valencia, Valencia, Spain. Electronic address: vmorenom@cipf.es.
Victoria
V
Moreno-Manzano
D000080:Acetals / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods
D000080:Acetals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D018696:Neuroprotective Agents; D011108:Polymers; C016067:polyacetal; D003474:Curcumin
Curcumin; Ependymal progenitor stem cells; Polymer Therapeutics; Rho kinase; Spinal cord injury