KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit
Abstract Background Urothelial regeneration is a crucial part of bladder tissue engineering. However, there is a lack of ideal “seed cells” in current practices. Here, we demonstrated that a sub-population of p63 positive basal cells could be activated and differentiate into intermediate and superfi...
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BMC
2025-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04417-z |
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| author | Jiasheng Chen Mingming Yu Lin Wang Hua Xie Yiqing Lv Yichen Huang Yue Hong Fang Chen |
| author_facet | Jiasheng Chen Mingming Yu Lin Wang Hua Xie Yiqing Lv Yichen Huang Yue Hong Fang Chen |
| author_sort | Jiasheng Chen |
| collection | DOAJ |
| description | Abstract Background Urothelial regeneration is a crucial part of bladder tissue engineering. However, there is a lack of ideal “seed cells” in current practices. Here, we demonstrated that a sub-population of p63 positive basal cells could be activated and differentiate into intermediate and superficial umbrella cells after full-thickness mucosal resection in rabbit. Methods A focal mucosal resection model was used to characterize the role of different urothelial cells during regeneration. Urothelial basal cells were isolated from rabbit bladder mucosa and cultured in vitro. The basal cells were then transplanted in vivo in a manner of cell sheet for reconstruction. Results Via single-cell RNA sequencing (scRNA-seq), it has been confirmed that the cluster of KRT5high TP63-expressing cells possesses a ‘‘stemness’’ signature which can give rise to lineage cell types sequentially. With a strong support from the underneath pre-set capsule vascular bed, the transplanted cell sheet could develop into a physio-morphology resembled to the native mucosa in vivo. Importantly, we validated that the bioengineered urothelium implemented perfect barrier function after implanted to bladder. Conclusions In summary, bioengineering urothelium with KRT5high TP63-expressing basal cells on a capsule vascular bed offers a promising strategy for bladder tissue engineering and provides a model for drug screening and bladder disease research. |
| format | Article |
| id | doaj-art-331c62dba5dd4a66818a94bfcfc3cb49 |
| institution | OA Journals |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-331c62dba5dd4a66818a94bfcfc3cb492025-08-20T02:31:03ZengBMCStem Cell Research & Therapy1757-65122025-06-0116111810.1186/s13287-025-04417-zKRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbitJiasheng Chen0Mingming Yu1Lin Wang2Hua Xie3Yiqing Lv4Yichen Huang5Yue Hong6Fang Chen7Department of Urology, School of Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityDepartment of Urology, School of Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityDepartment of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, School of Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityDepartment of Urology, School of Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityDepartment of Urology, School of Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityStem Cell Center, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, School of Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityAbstract Background Urothelial regeneration is a crucial part of bladder tissue engineering. However, there is a lack of ideal “seed cells” in current practices. Here, we demonstrated that a sub-population of p63 positive basal cells could be activated and differentiate into intermediate and superficial umbrella cells after full-thickness mucosal resection in rabbit. Methods A focal mucosal resection model was used to characterize the role of different urothelial cells during regeneration. Urothelial basal cells were isolated from rabbit bladder mucosa and cultured in vitro. The basal cells were then transplanted in vivo in a manner of cell sheet for reconstruction. Results Via single-cell RNA sequencing (scRNA-seq), it has been confirmed that the cluster of KRT5high TP63-expressing cells possesses a ‘‘stemness’’ signature which can give rise to lineage cell types sequentially. With a strong support from the underneath pre-set capsule vascular bed, the transplanted cell sheet could develop into a physio-morphology resembled to the native mucosa in vivo. Importantly, we validated that the bioengineered urothelium implemented perfect barrier function after implanted to bladder. Conclusions In summary, bioengineering urothelium with KRT5high TP63-expressing basal cells on a capsule vascular bed offers a promising strategy for bladder tissue engineering and provides a model for drug screening and bladder disease research.https://doi.org/10.1186/s13287-025-04417-zBladder urothelium regenerationUrothelial basal cellTissue engineeringCell sheetCapsule vascular bed |
| spellingShingle | Jiasheng Chen Mingming Yu Lin Wang Hua Xie Yiqing Lv Yichen Huang Yue Hong Fang Chen KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit Stem Cell Research & Therapy Bladder urothelium regeneration Urothelial basal cell Tissue engineering Cell sheet Capsule vascular bed |
| title | KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit |
| title_full | KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit |
| title_fullStr | KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit |
| title_full_unstemmed | KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit |
| title_short | KRT5high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit |
| title_sort | krt5high tp63 expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit |
| topic | Bladder urothelium regeneration Urothelial basal cell Tissue engineering Cell sheet Capsule vascular bed |
| url | https://doi.org/10.1186/s13287-025-04417-z |
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