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MP41-06: Multipotent adult progenitor cell treatment promotes bladder function recovery and decreases morbidity and duration of urinary tract infection in spinal cord injured rats

Saturday, May 13
3:30 PM - 5:30 PM
Location: BCEC: Room 156

Presentation Authors: James Jones*, Portland, OR, Marc DePaul, Cleveland, OH, MaiHua Zhu, Portland, OR, Bradley Lang, Cleveland, OH, Sarah Busch, Cleveland, OR, Cynthia Gregory, Michael Rutten, Lisa Buckley, Kenton Gregory, Hua Xie, Portland, OR

Introduction: Severe urinary tract infections (UTIs) in association with neurogenic bladder are common complications of spinal cord injury (SCI). In previous studies multipotent adult progenitor cell (MAPC®) treatment of SCI in rats improved locomotor and bladder (i.e., voiding volume and frequency) function recovery. This study investigated morbidity of UTIs following MAPC cell treatment of SCI in rats.

Methods: This study was a randomized, blinded, sham-controlled study in female Sprague-Dawley rats comparing intravenous treatment with 4 x 106 human MAPCs (n = 11) vs. saline (n = 11) at 24-hours post-SCI. Contusion SCI was induced at T8 using an Infinite Horizon Impactor (250 kilodyne impact). Bladders were manually expressed twice daily for 4 weeks post-SCI, and prophylactic antibiotic was administered for the first 5 days post-SCI. Rats with prolonged UTI symptoms or recurrent UTI episode received additional antibiotic treatment until the UTI resolved. The time and duration of the UTIs in the first 28 days post-SCI were recorded. Voiding frequency and volume were measured using metabolic cages at weeks 4, 6, 8 and 10 post-SCI.

Results: During the first 4 weeks post-SCI, only 3 of 11 (27%) MAPC cell -treated SCI rats compared to 8 of 11 (73%) saline-treated SCI rats had prolonged UTIs or recurrent episodes that needed additional antibiotic treatment (p = 0.03, Chi-sq). The duration of UTI was significantly shortened with the MAPC cell treatment compared to the saline treatment (2.4 vs. 5.4 days, p = 0.03, t-test). The MAPC cell-treated rats showed significant improvement in bladder function, evidenced by decreased voiding volume (p < 0.05, Fisher LSD, at week 8) and increased voiding frequency (p = 0.05, t-test, at week 4) compared to the saline-treated controls.

Conclusions: To our knowledge, this is the first report of MAPC cell treatment decreasing the morbidity and duration of UTIs in rats with SCI. MAPC cell treatment may decrease UTIs as a result of the positive effect of treatment on voiding volume and frequency, though the decrease in UTIs occurred prior to the measurement of improvement in voiding volume and frequency makes it possible that MAPC cell treatment may decrease UTIs through a mechanism distinct from or in addition to their positive impact on bladder function (e.g., MAPC cells may enhance anti-bacterial immunity, thereby reducing UTIs). These results suggest that MAPC cell treatment of SCI patients may decrease their UTIs, improving quality of life.

Source Of Funding: DARPA: W911NF-15-1-0074

James M. Jones

Oregon Health and Science University

James McAndrew Jones, B.A. (Andrew) is a Research Assisstant at the Oregon Health and Science University's Center from Regenerative Medicine. After completing his thesis and graduating from the University of Oregon Clark Honors College with a double major in history and Chinese, Mr. Jones turned his attention to the sciences, and began to pursue a career in medicine. Under Dr. Kenton Gregory and Dr. Hua Xie, he has worked on translational research projects in diverse topics including the development of novel devices to control hemmorhage in both the gastric and urinary tract, novel biomaterials to assisst in targeted cell therapy, and assays to rapidly assess the potency of adult stem cells. His primary focus has been in nerve & spinal cord injury, where he is conducting research in the use of cell therapy to minimize inflammatory damage after spinal cord contusion injury.

Outside of medical research, Mr. Jones is currently pursing entrance into medical school, as well as numerous hobbies. He speaks fluent Mandarin Chinese and has lived, worked and traveled in mainland China for over two years. In his free time, Mr. Jones enjoys heading out to explore Oregon's diverse landscape, where he enjoys hiking, skiing and just about everything else.

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MP41-06: Multipotent adult progenitor cell treatment promotes bladder function recovery and decreases morbidity and duration of urinary tract infection in spinal cord injured rats



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