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Marc DePaul ETD.pdf (81.63 MB)

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INTRAVENOUS MULTIPOTENT ADULT PROGENITOR CELL TREATMENT DECREASES INFLAMMATION LEADING TO FUNCTIONAL RECOVERY FOLLOWING SPINAL CORD INJURY

DePaul, Marc A
http://rave.ohiolink.edu/etdc/view?acc_num=case1451317702

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We develop here a contusion model of SCI to investigate the capacity of adult bone marrow-derived stem cells, termed multipotent adult progenitor cells (MAPCs), to alter inflammation and promote recovery following SCI. MAPCs were derived from human or rat donors and delivered either locally to the lesion or systemically via intravenous injection immediately following injury. Rats receiving intravenous human MAPCs displayed greater recovery in locomotion than animals treated with rat MAPCs or MAPCs of either origin delivered to the lesion. Delaying intravenous administration of human MAPCs by one day further improved locomotor recovery and significantly enhanced lower urinary tract recovery, re-establishing coordination between the detrusor and external urethral sphincter muscles. 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. Nonetheless, in the injured cord of treated animals we observed a decrease in macrophage number and activation, which was associated with significant sparing of neural tissue. In vitro, we show that human MAPCs have the ability to modulate macrophage activation, and prior exposure of macrophages to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Our results demonstrate that a single intravenous dose of human MAPCs one day following severe contusive SCI attenuates immune mediated secondary spinal cord injury, resulting in significant neural tissue sparing and substantial improvements in locomotor and lower urinary tract function. This preclinical study provides strong support for the use of MAPC therapy in acute human contusive SCI.
Jerry Silver (Advisor)
Richard Zigmond (Committee Chair)
Robert Miller (Committee Member)
Thomas Dick (Committee Member)
Yu-Shang Lee (Committee Member)
229 p.
Biology; Biomedical Engineering; Biomedical Research; Immunology; Neurobiology; Neurosciences
Neuroscience; spinal cord injury; bladder; spleen; macrophage; monocyte; stem cells; immune modulation; microarray; urodynamics; cystometrography; foxp3

Recommended Citations

Citations

  • DePaul, M. A. (2015). INTRAVENOUS MULTIPOTENT ADULT PROGENITOR CELL TREATMENT DECREASES INFLAMMATION LEADING TO FUNCTIONAL RECOVERY FOLLOWING SPINAL CORD INJURY [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1451317702

    APA Style (7th edition)

  • DePaul, Marc. INTRAVENOUS MULTIPOTENT ADULT PROGENITOR CELL TREATMENT DECREASES INFLAMMATION LEADING TO FUNCTIONAL RECOVERY FOLLOWING SPINAL CORD INJURY. 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1451317702.

    MLA Style (8th edition)

  • DePaul, Marc. "INTRAVENOUS MULTIPOTENT ADULT PROGENITOR CELL TREATMENT DECREASES INFLAMMATION LEADING TO FUNCTIONAL RECOVERY FOLLOWING SPINAL CORD INJURY." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1451317702

    Chicago Manual of Style (17th edition)

case1451317702
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© 2015, some rights reserved.Creative Commons License INTRAVENOUS MULTIPOTENT ADULT PROGENITOR CELL TREATMENT DECREASES INFLAMMATION LEADING TO FUNCTIONAL RECOVERY FOLLOWING SPINAL CORD INJURY by Marc A DePaul is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.