한빛사논문
Seung-Gyu Cha1†, Won-Kyu Rhim1†, Jun Yong Kim1,2,3†, Eun Hye Lee4, Seung Yeon Lee1, Jeong Min Park1, Jeoung Eun Lee5, Hyeji Yoon7, Chun Gwon Park2,3, Bum Soo Kim4,6, Tae Gyun Kwon4,6, Youngmi Lee7, Dong Ryul Lee1,5 and Dong Keun Han1*
1Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam- si 13488, Gyeonggi-do, Republic of Korea
2Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si 16419, Gyeonggi-do, Republic of Korea
3Intelligent Precision of Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangangu, Suwon-si 16419, Gyeonggi-do, Republic of Korea
4Joint Institute for Regenerative Medicine, Kyungpook National University, Jung-gu, Daegu 41944, Republic of Korea
5Bundang Medical Center, CHA Advanced Research Institute, CHA University, Sungnam- si 13488, Gyeonggi-do, Republic of Korea
6Department of Urology, School of Medicine, Kyungpook National University, Jung-gu, Daegu 41944, Republic of Korea
7Department of Chemistry and Nanoscience, Ewha Womans University, Seodaemun-gu, Seoul, Republic of Korea
†Seung-Gyu Cha, Won-Kyu Rhim and Jun Yong Kim contributed equally to this work.
*Correspondence: Dong Keun Han
Abstract
Background: To overcome the limitations of current alternative therapies for chronic kidney disease (CKD), tissue engineering-mediated regeneration strategies have demonstrated the possibilities for complete kidney tissue regeneration. Given the challenges associated with the reproducibility of renal basal cells, the incorporation of intermediate mesoderm (IM) cells and bioactive materials to control bioactivities of cells with supported scaffolds should be considered as a viable approach to enable the regeneration of the complex kidney structure via renal differentiation.
Methods: We developed PMEZ scaffolds by combining crucial bioactive components, such as ricinoleic acid-grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) integrated into biodegradable porous PLGA (P) platform. Additionally, we utilized differentiating extracellular vesicles (dEV) isolated during intermediate mesoderm differentiation into kidney progenitor cells, and IM cells were serially incorporated to facilitate kidney tissue regeneration through their differentiation into kidney progenitor cells in the 3/4 nephrectomy mouse model.
Results: The use of differentiating extracellular vesicles facilitated IM differentiation into kidney progenitor cells without additional differentiation factors. This led to improvements in various regeneration-related bioactivities including tubule and podocyte regeneration, anti-fibrosis, angiogenesis, and anti-inflammation. Finally, implanting PMEZ/dEV/IM scaffolds in mouse injury model resulted in the restoration of kidney function.
Conclusions: Our study has demonstrated that utilizing biodegradable PLGA-based scaffolds, which include multipotent cells capable of differentiating into various kidney progenitor cells along with supporting components, can facilitate kidney tissue regeneration in the mouse model that simulates CKD through 3/4 nephrectomy.
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