title: Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury.
abstract: Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI. In vitro, we show that human multipotent adult progenitor cells (MAPCs) have the ability to modulate macrophage activation, and prior exposure to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Using a contusion model of SCI, we found that intravenous delivery of MAPCs one day, but not immediately, after SCI significantly improves urinary and locomotor recovery, which was associated with marked spinal cord tissue sparing. Intravenous MAPCs altered the immune response in the spinal cord and periphery, however biodistribution studies revealed that no MAPCs were found in the cord and instead preferentially homed to the spleen. Our results demonstrate that MAPCs exert their primary effects in the periphery and provide strong support for the use of these cells in acute human contusive SCI.
authors.affiliation: Case Western Reserve Univ., Dept. of Neurosciences, 10900 Euclid Ave., SOM E654, Cleveland, OH, 44106, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: DePaul
authors.affiliation: Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Palmer
authors.affiliation: Case Western Reserve Univ., Dept. of Neurosciences, 10900 Euclid Ave., SOM E654, Cleveland, OH, 44106, USA.|Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Lang
authors.affiliation: Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Cutrone
authors.affiliation: Case Western Reserve Univ., Dept. of Neurosciences, 10900 Euclid Ave., SOM E654, Cleveland, OH, 44106, USA.
authors.forename: Amanda P
authors.initials: AP
authors.lastname: Tran
authors.affiliation: Case Western Reserve Univ., Dept. of Neurosciences, 10900 Euclid Ave., SOM E654, Cleveland, OH, 44106, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Madalena
authors.affiliation: ReGenesys, Bioincubator Leuven, 3001, Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Bogaerts
authors.affiliation: Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hamilton
authors.affiliation: Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Deans
authors.affiliation: Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mays
authors.affiliation: Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Busch
authors.affiliation: Case Western Reserve Univ., Dept. of Neurosciences, 10900 Euclid Ave., SOM E654, Cleveland, OH, 44106, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Silver
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D001119:Arginase / Q000378:metabolism; D001369:Axons / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000628:therapy*; D007275:Injections, Intravenous; D008264:Macrophages / Q000473:pathology; D009043:Motor Activity; D039902:Multipotent Stem Cells / Q000166:cytology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy*; D033581:Stem Cell Transplantation; D014018:Tissue Distribution; D014554:Urination
chemical_list: D052247:Nitric Oxide Synthase Type II; D001119:Arginase