Renal subcapsular delivery of PGE2 promotes kidney repair by activating endogenous Sox9+ stem cells
Shang Chen,
Haoyan Huang,
Yue Liu,
Chen Wang,
Xiaoniao Chen,
Yuqiao Chang,
Yuhao Li,
Zhikun Guo,
Zhibo Han,
Zhong-Chao Han,
Qiang Zhao,
Xiang-Mei Chen,
Zongjin Li
Affiliations
Shang Chen
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Sciences, Tianjin, China
Haoyan Huang
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Sciences, Tianjin, China
Yue Liu
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China
Chen Wang
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China
Xiaoniao Chen
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Yuqiao Chang
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
Yuhao Li
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China
Zhikun Guo
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
Zhibo Han
Jiangxi Engineering Research Center for Stem Cell, Shangrao, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center for Cell Products, AmCellGene Co., Ltd., Tianjin China
Zhong-Chao Han
Jiangxi Engineering Research Center for Stem Cell, Shangrao, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center for Cell Products, AmCellGene Co., Ltd., Tianjin China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing, China
Qiang Zhao
The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Sciences, Tianjin, China
Xiang-Mei Chen
State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100039, China; Corresponding author
Zongjin Li
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Sciences, Tianjin, China; Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China; State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100039, China; Corresponding author
Summary: Prostaglandin E2 (PGE2) has recently been recognized to play a role in immune regulation and tissue regeneration. However, the short half-life of PGE2 limits its clinical application. Improving the delivery of PGE2 specifically to the target organ with a prolonged release method is highly desirable. Taking advantage of the adequate space and proximity of the renal parenchyma, renal subcapsular delivery allows minimally invasive and effective delivery to the entire kidney. Here, we report that by covalently cross-linking it to a collagen matrix, PGE2 exhibits an adequate long-term presence in the kidney with extensive intraparenchymal penetration through renal subcapsular delivery and significantly improves kidney function. Sox9 cell lineage tracing with intravital microscopy revealed that PGE2 could activate the endogenous renal progenitor Sox9+ cells through the Yap signaling pathway. Our results highlight the prospects of utilizing renal subcapsular-based drug delivery and facilitate new applications of PGE2-releasing matrices for regenerative therapy.
