Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

Marc A DePaul of Case Western Reserve University

Marc A DePaul of Case Western Reserve University

Following spinal cord injury (SCI), immune-mediated secondary injury exacerbates the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammatory processes 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.

DePaul, M. A. et al. Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury. Sci. Rep. 5, 16795; doi: 10.1038/srep16795 (2015).

Read the Full Open Article HERE at Nature Scientific Reports

Neuroscience News Article

Marc A. DePaul1, Marc Palmer2, Bradley T. Lang1,2, Rochelle Cutrone2, Amanda P. Tran1,Kathryn M. Madalena1, Annelies Bogaerts3, Jason A. Hamilton2, Robert J. Deans2,Robert W. Mays2, Sarah A. Busch2 & Jerry Silver1

1Case Western Reserve Univ., Dept. of Neurosciences, 10900 Euclid Ave., SOM E654, Cleveland, OH, 44106, USA.2Athersys, Inc. Regenerative Medicine, Cleveland, OH, 44115, USAs. 3ReGenesys, Bioincubator Leuven, 3001,Leuven, Belgium.

Acknowledgements: The authors thank the Spinal Cord Injury Research Training Program at Ohio State University for surgical and behavioral training and guidance, and Jared Cregg, Yu-Shang Lee, JingQiang You, Warren Alilain, Sarah Zilka Starke, and Anthony Ting for their valuable input into the project. This work was supported by an Ohio Third Frontier Grant to the National Center for Regenerative Medicine, National Institute of Neurological Disorders and Stroke grant NS025713 (J.S.); the Case Western Reserve University Council to Advance Human Health; P. Jing, R. Senior and S. Poon; Unite to Fight Paralysis; The Brumagin Memorial Fund; Spinal Cord Injury Sucks; United Paralysis Foundation; and The Kaneko Family Fund.

Athersys Press Release:

This study builds on a decade-long collaboration between Athersys and Case Western Reserve University School of Medicine, led by Professor Jerry Silver, Ph.D., of the Department of Neurosciences. Dr. Silver stated, “Spinal cord injury continues to devastate the lives of many. Although a great deal of research needs to be undertaken in the field, we are pleased to see that MultiStem therapy is efficacious in promoting the recovery of locomotor and urinary functions in rodents. I am especially excited with this therapy as it circumvents the need for directed therapeutic delivery into the vulnerable, recently injured spinal cord. We look forward to working with Athersys and other leaders in the science community to fill this critical treatment gap.”

This study provides additional strong support for the use of MultiStem as a therapeutic for human acute spinal cord injury with the overall goals of improving quality of life, motor control, and reducing long-term patient care costs. According to the Christopher and Dana Reeve Foundation, the cost of spinal cord injury is estimated to be from $500,000 to more than $3 million per patient, depending on severity. Donna Sullivan, Project Director for Unite 2 Fight Paralysis, commented, “We are excited by these results in rodent models of spinal cord injury, which demonstrate that MultiStem therapy may have the potential to enhance patients’ lives by improving critical locomotor and bladder functions. Improvement in these functions will reduce the many life threatening secondary conditions, which are a result of the loss of these functions. Unite 2 Fight Paralysis looks forward to additional opportunities to partner with this team of scientists to bring this cell therapy to the bedside.”

The research was coordinated by Dr. Sarah Busch and other Athersys scientists in collaboration with Dr. Jerry Silver, graduate student Marc DePaul, and other scientists from Case Western Reserve University School of Medicine, with grant support from The Ohio Third Frontier.

Additional information about MAPC from Athersys can be found HERE.

Stem cell treatment mediates immune response to spinal cord injury in pre-clinical trials: Case Western Reserve University

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