title: Bone Marrow Stromal Cell Intraspinal Transplants Fail to Improve Motor Outcomes in a Severe Model of Spinal Cord Injury.
abstract: Bone marrow stromal cells (BMSCs) have been reported to exert potential neuroprotective properties in models of neurotrauma, although precise mechanisms underlying their benefits are poorly understood. Despite this lack of knowledge, several clinical trials have been initiated using these cells. To determine whether local mechanisms mediate BMSC neuroprotective actions, we grafted allogeneic BMSCs to sites of severe, compressive spinal cord injury (SCI) in Sprague-Dawley rats. Cells were administered 48 h after the original injury. Additional animals received allogeneic MSCs that were genetically modified to secrete brain-derived neurotrophic factor (BDNF) to further determine whether a locally administered neurotrophic factor provides or extends neuroprotection. When assessed 2 months post-injury in a clinically relevant model of severe SCI, BMSC grafts with or without BDNF secretion failed to improve motor outcomes. Thus, allogeneic grafts of BMSCs do not appear to act through local mechanisms, and future clinical trials that acutely deliver BMSCs to actual sites of injury within days are unlikely to be beneficial. Additional studies should address whether systemic administration of BMSCs alter outcomes from neurotrauma.
authors.affiliation: 1 Department of Neurosciences, University of California , San Diego, La Jolla, California.|2 Veterans Administration San Diego Healthcare System , La Jolla, California.
authors.forename: John H
authors.initials: JH
authors.lastname: Brock
authors.affiliation: 1 Department of Neurosciences, University of California , San Diego, La Jolla, California.
authors.forename: Lori
authors.initials: L
authors.lastname: Graham
authors.affiliation: 1 Department of Neurosciences, University of California , San Diego, La Jolla, California.
authors.forename: Eileen
authors.initials: E
authors.lastname: Staufenberg
authors.affiliation: 1 Department of Neurosciences, University of California , San Diego, La Jolla, California.
authors.forename: Eileen
authors.initials: E
authors.lastname: Collyer
authors.affiliation: 1 Department of Neurosciences, University of California , San Diego, La Jolla, California.
authors.forename: Jacob
authors.initials: J
authors.lastname: Koffler
authors.affiliation: 1 Department of Neurosciences, University of California , San Diego, La Jolla, California.|2 Veterans Administration San Diego Healthcare System , La Jolla, California.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D017154:Stromal Cells / Q000637:transplantation*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: bone marrow stromal cells; brain-derived neurotrophic factor; neuroprotection; severe spinal cord compression