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

© 2023. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:27

Enthalten in:

Biomaterials research - 27(2023), 1 vom: 05. Dez., Seite 126

Sprache:

Englisch

Beteiligte Personen:

Cha, Seung-Gyu [VerfasserIn]
Rhim, Won-Kyu [VerfasserIn]
Kim, Jun Yong [VerfasserIn]
Lee, Eun Hye [VerfasserIn]
Lee, Seung Yeon [VerfasserIn]
Park, Jeong Min [VerfasserIn]
Lee, Jeoung Eun [VerfasserIn]
Yoon, Hyeji [VerfasserIn]
Park, Chun Gwon [VerfasserIn]
Kim, Bum Soo [VerfasserIn]
Kwon, Tae Gyun [VerfasserIn]
Lee, Youngmi [VerfasserIn]
Lee, Dong Ryul [VerfasserIn]
Han, Dong Keun [VerfasserIn]

Links:

Volltext

Themen:

Differentiating extracellular vesicle (dEV)
Intermediate mesoderm (IM)
Journal Article
Kidney differentiation
Kidney tissue regeneration
PMEZ scaffold

Anmerkungen:

Date Revised 07.12.2023

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1186/s40824-023-00471-x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365408271