Tissue Eng Regen Med.  2022 Jun;19(3):643-658. 10.1007/s13770-022-00442-8.

Improvement of IgA Nephropathy and Kidney Regeneration by Functionalized Hyaluronic Acid and Gelatin Hydrogel

Affiliations
  • 1Department of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 06974, Korea
  • 2BioMedical Research Institute, Kyungpook National University Hospital, Daegu 41940, Korea
  • 3Department of Urology, Kyungpook National University Hospital, Daegu 41944, Korea
  • 4Department of Urology, Kyungpook National University Chilgok Hospital, Daegu 41404, Korea
  • 5Department of Urology, School of Medicine, Kyungpook National University, Daegu 41566, Korea
  • 6Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-go, Seoul 02841, Korea

Abstract

BACKGROUND
Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water. Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN.
METHODS
CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration.
RESULTS
The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group.
CONCLUSION
Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

Keyword

Injectable hydrogel; Injectable hydrogel; Urine-derived renal progenitor cells; Urine-derived renal progenitor cells; IgA nephropathy; IgA nephropathy
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