Login to Access Video or Poster Abstract: MP41-06
Sources of Funding: DARPA: W911NF-15-1-0074

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.

Funding

DARPA: W911NF-15-1-0074