Biofabricated Adipose-Derived Mesenchymal Cell Sheets Recover Cryo-Injured Kidneys in Rats.

Area of Science:

• Regenerative Medicine
• Nephrology
• Biomaterials Engineering

Background:

• Chronic kidney disease (CKD) poses a significant global health burden.
• Current treatments for CKD are limited and often focus on slowing disease progression rather than regeneration.
• Adipose-derived mesenchymal cells (AMCs) show promise for tissue repair due to their regenerative and immunomodulatory properties.

Purpose of the Study:

• To develop and evaluate biofabricated adipose-derived mesenchymal cell (AMC) sheets as a potential treatment for chronic kidney disease (CKD).
• To assess the efficacy of AMC sheets in improving renal tissue structure and function following cryo-injury in a rat model.

Main Methods:

• Biofabrication of bilayered AMC-gelatin sheets using cultured AMCs on temperature-responsive dishes and gelatin hydrogel.
• Autologous transplantation of AMC sheets into the renal capsule of cryo-injured kidneys in Sprague-Dawley rats.
• Assessment of renal function via creatinine clearance and serum creatinine levels, alongside histological and molecular analyses.

Main Results:

• AMC sheet transplantation significantly increased creatinine clearance and maintained normal serum creatinine levels compared to acellular controls.
• Histological analysis revealed reduced renal tubule damage and lower fibrotic area occupancy in AMC-treated kidneys.
• Reduced expression of TGF-β1 and HIF-1α, and detection of vascular endothelial growth factor (VEGF) in transplanted AMCs were observed.

Conclusions:

• Biofabricated AMC sheets effectively ameliorated renal tubule disorders and fibrosis in a CKD rat model.
• Transplanted AMCs integrated into the renal tissue and exhibited regenerative potential.
• Biofabricated AMC sheets represent a promising therapeutic strategy for managing and potentially treating chronic kidney disease.