Kidney tissue regeneration using bioactive scaffolds incorporated with differentiating extracellular vesicles and intermediate mesoderm cells

• Published in: Biomaterials research Vol. 27; no. 1; pp. 1 - 2893
• Main Authors: Cha, Seung-Gyu, Rhim, Won-Kyu, Kim, Jun Yong, Lee, Eun Hye, Lee, Seung Yeon, Park, Jeong Min, Lee, Jeoung Eun, Yoon, Hyeji, Park, Chun Gwon, Kim, Bum Soo, Kwon, Tae Gyun, Lee, Youngmi, Lee, Dong Ryul, Han, Dong Keun
• Format: Journal Article
• Language: English
• Published: London BioMed Central 05.12.2023; BioMed Central Ltd; 한국생체재료학회
• Subjects: Acids; Analysis; Angiogenesis; Basal cells; Biocompatibility; Biodegradability; Biomaterials; Cell culture; Cell differentiation; Cell growth; Chemistry and Materials Science; Chronic kidney failure; Extracellular matrix; Extracellular vesicles; Fibrosis; Kidney diseases; Lipoic acid; Magnesium; Materials Science; Mesoderm; Nephrectomy; Nitric oxide; Polylactide-co-glycolide; Progenitor cells; Regenerative medicine; Research Article; Ricinoleic acid; Stem cells; Tissue engineering; Zinc oxides; 의공학; South Korea; United States > US; Intermediate mesoderm (IM); Differentiating extracellular vesicle (dEV); Kidney differentiation; PMEZ scaffold; Kidney tissue regeneration
• ISSN: 2055-7124; 1226-4601; 2055-7124
• DOI: 10.1186/s40824-023-00471-x

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. Graphical Abstract