Sureerat Khunmanee1, So Young Chun2, Yun-Sok Ha3,4, Jun Nyung Lee3,5, Bum Soo Kim3,5, Wei-Wei Gao6, In Yong Kim6, Dong Keun Han7, Seungkwon You6, Tae Gyun Kwon8,9, Hansoo Park10. 1. Department of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul, 06974, Korea. 2. BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41940, Korea. 3. Department of Urology, Kyungpook National University Hospital, Daegu, 41944, Korea. 4. Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, 41404, Korea. 5. Department of Urology, School of Medicine, Kyungpook National University, Daegu, 41566, Korea. 6. Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-go, Seoul, 02841, Korea. 7. Department of Biomedical Science, College of Life Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi, 13488, Korea. 8. Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, 41404, Korea. tgkwon@knu.ac.kr. 9. Department of Urology, School of Medicine, Kyungpook National University, Daegu, 41566, Korea. tgkwon@knu.ac.kr. 10. Department of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul, 06974, Korea. heyshoo@cau.ac.kr.
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 pro-fibrotic 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.
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 pro-fibrotic 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.
Authors: Elena Lazzeri; Elisa Ronconi; Maria Lucia Angelotti; Anna Peired; Benedetta Mazzinghi; Francesca Becherucci; Sara Conti; Giulia Sansavini; Alessandro Sisti; Fiammetta Ravaglia; Duccio Lombardi; Aldesia Provenzano; Anna Manonelles; Josep M Cruzado; Sabrina Giglio; Rosa Maria Roperto; Marco Materassi; Laura Lasagni; Paola Romagnani Journal: J Am Soc Nephrol Date: 2015-01-07 Impact factor: 10.121
Authors: Elena Martínez-Sanz; Dmitri A Ossipov; Jöns Hilborn; Sune Larsson; Kenneth B Jonsson; Oommen P Varghese Journal: J Control Release Date: 2011-02-22 Impact factor: 9.776
Authors: Young Youl Hyun; In Ok Kim; Mi Hyung Kim; Deok Hwa Nam; Mi Hwa Lee; Jung Eun Kim; Hye Kyoung Song; Jin Joo Cha; Young Sun Kang; Ji Eun Lee; Hyun Wook Kim; Jee Young Han; Dae Ryong Cha Journal: Cell Transplant Date: 2012-04-17 Impact factor: 4.064
Authors: Patrícia de Carvalho Ribeiro; Fernando Henrique Lojudice; Ida Maria Maximina Fernandes-Charpiot; Maria Alice Sperto Ferreira Baptista; Stanley de Almeida Araújo; Gloria Elisa Florido Mendes; Mari Cleide Sogayar; Mario Abbud-Filho; Heloisa Cristina Caldas Journal: Stem Cell Res Ther Date: 2020-12-09 Impact factor: 6.832