Anna Burdzinska1, Bartosz Dybowski2, Weronika Zarychta-Wiśniewska1, Agnieszka Kulesza1, Jakub Hawryluk1, Agnieszka Graczyk-Jarzynka3, Patryk Kaupa4, Zdzislaw Gajewski5, Leszek Paczek1,6. 1. Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland. 2. Department of Urology, Medical University of Warsaw, Warsaw, Poland. 3. Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland. 4. Other Gravity Sp.zo.o., Warsaw, Poland. 5. Department of Large Animal Diseases with Clinic, Veterinary Research Centre and Center for Biomedical Research, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), Warsaw, Poland. 6. Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Abstract
AIMS: The efficacy of cell therapy in patients with stress urinary incontinence (SUI) is lower than expected. The aim of this study was to determine the injection accuracy rate both with transurethral and periurethral route. METHODS: Autologous intraurethral cell transplantation was performed in female goats. The cells were injected either periurethrally (PERI group, two depots/animal, n = 8) or transurethrally (TRANS group, eight depots/animal, n = 11). Transurethral injections were performed under endoscopic guidance. The number and distribution of cell depots in urethras were analyzed in the three-step protocol: 1) screening of whole explants by in vivo imaging system; 2) systematic microscopic analysis of raw 10 μm cross-sections; 3) immunohistochemistry. As control, four urethras collected 1 day after transurethral transplantation were used. Episodes of cell suspension leakages after needle withdrawal were noted. RESULTS: In all experimental animals depots were identified in the urethral wall 28 days after transplantation. The mean percentage of depots located in the urethral wall in relation to all performed injections amounted to 68.7% and 67.0% for PERI and TRANS groups, respectively. The mean proportions of depots which were identified in external urethral sphincter (EUS) amounted 18.8% and 17.1%, respectively. Suspension leakage was observed in 19% of transurethral injections. CONCLUSIONS: Although majority of cell depots were administrated accurately into the urethral wall, the precise delivery of cells into EUS is limited regardless of injection method. The insufficient accuracy of cell delivery into EUS and cell suspension leakage can contribute to the low efficacy of cell therapy in human patients with SUI.
AIMS: The efficacy of cell therapy in patients with stress urinary incontinence (SUI) is lower than expected. The aim of this study was to determine the injection accuracy rate both with transurethral and periurethral route. METHODS: Autologous intraurethral cell transplantation was performed in female goats. The cells were injected either periurethrally (PERI group, two depots/animal, n = 8) or transurethrally (TRANS group, eight depots/animal, n = 11). Transurethral injections were performed under endoscopic guidance. The number and distribution of cell depots in urethras were analyzed in the three-step protocol: 1) screening of whole explants by in vivo imaging system; 2) systematic microscopic analysis of raw 10 μm cross-sections; 3) immunohistochemistry. As control, four urethras collected 1 day after transurethral transplantation were used. Episodes of cell suspension leakages after needle withdrawal were noted. RESULTS: In all experimental animals depots were identified in the urethral wall 28 days after transplantation. The mean percentage of depots located in the urethral wall in relation to all performed injections amounted to 68.7% and 67.0% for PERI and TRANS groups, respectively. The mean proportions of depots which were identified in external urethral sphincter (EUS) amounted 18.8% and 17.1%, respectively. Suspension leakage was observed in 19% of transurethral injections. CONCLUSIONS: Although majority of cell depots were administrated accurately into the urethral wall, the precise delivery of cells into EUS is limited regardless of injection method. The insufficient accuracy of cell delivery into EUS and cell suspension leakage can contribute to the low efficacy of cell therapy in humanpatients with SUI.
Authors: Walter Linzenbold; Andreas Fech; Manuela Hofmann; Wilhelm K Aicher; Markus D Enderle Journal: Int J Mol Sci Date: 2021-06-14 Impact factor: 5.923