Intravesical Administration of Xenogeneic Porcine Urothelial Cells Attenuates Cyclophosphamide-Induced Cystitis in Mice
| Autor: | Yi-Tung Tsai, Chi-Cheng Chen, Chih-Rong Shyr, Chi-Ping Huang, Chun-Chie Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Urothelial Cell Cyclophosphamide Cell Transplantation Swine Biomedical Engineering lcsh:Medicine Inflammation urologic and male genital diseases cyclophosphamide (CPP) Cell therapy 03 medical and health sciences intravesical Mice 0302 clinical medicine Cystitis medicine Animals Urothelium Progenitor cell bladder Transplantation porcine urothelial cell (PUC) business.industry xenogeneic lcsh:R Interstitial cystitis urothelium Cell Biology Original Articles medicine.disease female genital diseases and pregnancy complications Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Heterografts Female medicine.symptom business cytotherapy Hemorrhagic cystitis medicine.drug |
| Zdroj: | Cell Transplantation, Vol 28 (2019) Cell Transplantation |
| ISSN: | 1555-3892 0963-6897 |
| Popis: | The urothelium of the bladder, renal pelvis, ureter and urethra is maintained through the regulated proliferation and differentiation of urothelial stem and progenitor cells. These cells provide a rich source of a novel urothelial cell therapy approach that could be used to protect, regenerate, repair and restore a damaged urothelium. Urothelial injury caused by physical, chemical and microbial stress is the pathological basis of cystitis (bladder inflammation). The loss of urothelial integrity triggers a series of inflammatory events, resulting in pain and hematuria such as hemorrhage cystitis and interstitial cystitis. Here we investigate a novel cell therapy strategy to treat cystitis by protecting the urothelium from detrimental stresses through intravesically instilling porcine urothelial cells (PUCs) into the bladder. Using a chemical-induced urothelial injury mouse model of cyclophosphamide (CPP)-induced hemorrhagic cystitis, we determined how the intravesical instillation of PUCs could protect the urothelium from toxic attack from CPP metabolites. We show that intravesical PUC instillation protected the bladder from toxic chemical attack in mice receiving CPP with reduced inflammation and edema. Compared with the vehicle control mice, the proliferative response to chemical injury and apoptotic cells within the bladder tissues were reduced by intravesical PUC treatment. Furthermore, the urothelium integrity was maintained in the intravesical PUC-treated group. After xenogeneic PUCs were introduced and adhered to the mouse urothelium, immunological rejection responses were observed with increased neutrophil infiltration in the lamina propria and higher immune-related gene expression. Our findings provide an innovative and promising intravesical PUC cell therapy for cystitis with urothelial injury by protecting the urothelium from noxious agents. |
| Databáze: | OpenAIRE |
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