title: Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats.
abstract: Schwann cell (SC) transplantation exhibits significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 min or 1 week after SCI, could enhance the efficacy of SCs when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: J Bryan
authors.initials: JB
authors.lastname: Iorgulescu
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Samik P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Department of Anesthesiology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Louro
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Andrade
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Andre R
authors.initials: AR
authors.lastname: Sanchez
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; The Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D003131:Combined Modality Therapy; D003288:Contusions / Q000473:pathology; D005260:Female; D055104:Infusions, Subcutaneous; D008124:Locomotion; D009416:Nerve Regeneration; D011700:Putrescine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D020127:Recovery of Function; D012583:Schwann Cells / Q000637:transplantation*; D011984:Sensory Receptor Cells / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000628:therapy*
chemical_list: C491562:Crcp protein, rat; D018015:Receptors, Calcitonin Gene-Related Peptide; D012701:Serotonin; D011700:Putrescine