Department of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul, 06974, Korea.
BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41940, Korea.
Tissue Eng Regen Med. 2022 Jun;19(3):643-658. doi: 10.1007/s13770-022-00442-8. Epub 2022 Mar 24.
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-NH) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN.
CHO-HA/Gel-NH 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.
The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH 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 pro-fibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group.
Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.
免疫球蛋白 A (IgA) 肾病 (IgAN) 是导致进行性肾病的重要原因之一，当 IgA 在肾脏中沉淀导致肾脏过滤废物和多余水分的能力受损时，就会发生这种情况。水凝胶因其出色的适应性和填充能力而成为有前途的医学应用材料。在此，我们提出了一种透明质酸/明胶 (CHO-HA/Gel-NH) 生物活性水凝胶，作为 IgAN 治疗性肾脏再生的细胞载体。
通过席夫碱反应制备 CHO-HA/Gel-NH 水凝胶，无需任何额外的交联剂。评估水凝胶的浓度和比例，以增强足够的机械性能和生物相容性，以进行进一步的体内研究。用封装在水凝胶中的人尿源性肾祖细胞处理高血清 IgA ddY 小鼠的肾脏，以研究 IgA 肾病和肾脏再生的改善情况。
水凝胶的硬度通过改变水凝胶的浓度和比例得到显著增强，并可以进行调节。CHO-HA/Gel-NH 的比例为 3/7 为细胞活力和增殖提供了有前景的环境。从第 4 周开始，细胞/凝胶组的血尿素氮和血清肌酐水平显著降低，肾小球和肾小管排列整齐。此外，在凝胶/细胞组中，促炎和促纤维化分子的表达显著降低，而与细胞组相比，抗炎基因的表达升高。
基于体内研究，该水凝胶系统可进一步增强祖细胞的肾脏再生能力。
