Yuan-Hong Jiang1, Jia-Fong Jhang1, Yung-Hsiang Hsu2, Han-Chen Ho3, Teng-Yi Lin4, Lori A Birder5, Hann-Chorng Kuo1. 1. Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. 2. Department of Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. 3. Department of Anatomy, Tzu Chi University, Hualien, Taiwan. 4. Department Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. 5. Departments of Medicine; Pharmacology, and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract
OBJECTIVE: This clinical study used autologous intravesical platelet-rich plasma (PRP) injections to treat patients with recurrent urinary tract infection (rUTI). Changes in urothelial proliferation, cytoskeleton, and barrier function protein expression after treatment were investigated. MATERIALS: All patients underwent 4-monthly intravesical PRP injections with 1-year follow-up. Successful treatment was defined as ≤2 UTI episodes within the preceding 1 year. Bladder biopsies were performed at the first and fourth PRP injection, and specimens were investigated by Western blot for the proteins sonic hedgehog (Shh), CD34, cytokeratin 5 (CK5), CK14, CK20, zonula occludens-1 (ZO-1), E-cadherin, inflammatory proteins tryptase and p38, apoptotic protein BAX (BCL2-associated X protein) and caspase-3, functional proteins M2 (muscarinic receptor 2) and M3, and beta-adrenoceptor-3, with glyceraldehyde phosphate dehydrogenase used as normalizing protein for quantification. RESULTS: The study enrolled 22 patients with rUTI and 17 controls, with successful outcome in 14 of 22 (63.6%) patients. Compared with controls, Western blot quantification results showed that rUTI patients had lower CD34, CK20, M3, and ZO-1, but higher CK5, BAX, and caspase-3 at baseline. The reduced CD34, CK20, M2, and M3 expressions at baseline were significantly increased after repeat PRP injections. Patients with a successful outcome had significant increase of CD34, Shh, CK20, M2, and M3 expressions after PRP injections. CONCLUSION: Intravesical PRP repeat injections improve the urothelial cell proliferation and increase the CK 20 expression in umbrella cells. PRP repeat injections have a beneficial effect on bladder urothelium-associated changes in rUTI. Thus, PRP injection may restore urothelial health and prevent UTI recurrence in intractable rUTI.
OBJECTIVE: This clinical study used autologous intravesical platelet-rich plasma (PRP) injections to treat patients with recurrent urinary tract infection (rUTI). Changes in urothelial proliferation, cytoskeleton, and barrier function protein expression after treatment were investigated. MATERIALS: All patients underwent 4-monthly intravesical PRP injections with 1-year follow-up. Successful treatment was defined as ≤2 UTI episodes within the preceding 1 year. Bladder biopsies were performed at the first and fourth PRP injection, and specimens were investigated by Western blot for the proteins sonic hedgehog (Shh), CD34, cytokeratin 5 (CK5), CK14, CK20, zonula occludens-1 (ZO-1), E-cadherin, inflammatory proteins tryptase and p38, apoptotic protein BAX (BCL2-associated X protein) and caspase-3, functional proteins M2 (muscarinic receptor 2) and M3, and beta-adrenoceptor-3, with glyceraldehyde phosphate dehydrogenase used as normalizing protein for quantification. RESULTS: The study enrolled 22 patients with rUTI and 17 controls, with successful outcome in 14 of 22 (63.6%) patients. Compared with controls, Western blot quantification results showed that rUTI patients had lower CD34, CK20, M3, and ZO-1, but higher CK5, BAX, and caspase-3 at baseline. The reduced CD34, CK20, M2, and M3 expressions at baseline were significantly increased after repeat PRP injections. Patients with a successful outcome had significant increase of CD34, Shh, CK20, M2, and M3 expressions after PRP injections. CONCLUSION: Intravesical PRP repeat injections improve the urothelial cell proliferation and increase the CK 20 expression in umbrella cells. PRP repeat injections have a beneficial effect on bladder urothelium-associated changes in rUTI. Thus, PRP injection may restore urothelial health and prevent UTI recurrence in intractable rUTI.