Functional Kidney Bioengineering with Pluripotent Stem-Cell-Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds

被引:53
作者
Du, Chan [1 ]
Narayanan, Karthikeyan [1 ]
Leong, Meng Fatt [1 ]
Ibrahim, Mohammed Shahrudin [1 ]
Chua, Ying Ping [1 ]
Khoo, Vanessa Mei Hui [1 ]
Wan, Andrew C. A. [1 ]
机构
[1] Inst Bioengn & Nanotechnol, 31 Biopolis Way, Singapore 138669, Singapore
关键词
cellular self-assembly; decellularized ECM scaffold; endothelial cells; kidney tissue engineering; renal progenitors; EXTRACELLULAR-MATRIX SCAFFOLDS; BIOARTIFICIAL KIDNEY; ENDOTHELIAL-CELLS; DIFFERENTIATION; TRANSPLANTATION; REGENERATION; ORGANOIDS; LIVER;
D O I
10.1002/adhm.201600120
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney.
引用
收藏
页码:2080 / 2091
页数:12
相关论文
共 37 条
[1]   A 3-D organoid kidney culture model engineered for high-throughput nephrotoxicity assays [J].
Astashkina, Anna I. ;
Mann, Brenda K. ;
Prestwich, Glenn D. ;
Grainger, David W. .
BIOMATERIALS, 2012, 33 (18) :4700-4711
[2]  
Bonandrini B, 2014, TISSUE ENG PT A, V20, P1486, DOI [10.1089/ten.TEA.2013.0269, 10.1089/ten.tea.2013.0269]
[3]   Nephric lineage specification by Pax2 and Pax8 [J].
Bouchard, M ;
Souabni, A ;
Mandler, M ;
Neubüser, A ;
Busslinger, M .
GENES & DEVELOPMENT, 2002, 16 (22) :2958-2970
[4]   Regulatory molecules in kidney development [J].
Burrow, CR .
PEDIATRIC NEPHROLOGY, 2000, 14 (03) :240-253
[5]   Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds as Biological Templates for Organ Engineering and Transplantation [J].
Caralt, M. ;
Uzarski, J. S. ;
Iacob, S. ;
Obergfell, K. P. ;
Berg, N. ;
Bijonowski, B. M. ;
Kiefer, K. M. ;
Ward, H. H. ;
Wandinger-Ness, A. ;
Miller, W. M. ;
Zhang, Z. J. ;
Abecassis, M. M. ;
Wertheim, J. A. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2015, 15 (01) :64-75
[6]   Cell-Cell Interactions Driving Kidney Morphogenesis [J].
Combes, Alexander N. ;
Davies, Jamie A. ;
Little, Melissa H. .
CELLULAR ADHESION IN DEVELOPMENT AND DISEASE, 2015, 112 :467-508
[7]   Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering [J].
Du, Chan ;
Narayanan, Karthikeyan ;
Leong, Meng Fatt ;
Wan, Andrew C. A. .
BIOMATERIALS, 2014, 35 (23) :6006-6014
[8]   Self-organizing optic-cup morphogenesis in three-dimensional culture [J].
Eiraku, Mototsugu ;
Takata, Nozomu ;
Ishibashi, Hiroki ;
Kawada, Masako ;
Sakakura, Eriko ;
Okuda, Satoru ;
Sekiguchi, Kiyotoshi ;
Adachi, Taiji ;
Sasai, Yoshiki .
NATURE, 2011, 472 (7341) :51-U73
[9]   Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis [J].
Georges, Penelope C. ;
Hui, Jia-Ji ;
Gombos, Zoltan ;
McCormick, Margaret E. ;
Wang, Andrew Y. ;
Uemura, Masayuki ;
Mick, Rosemarie ;
Janmey, Paul A. ;
Furth, Emma E. ;
Wells, Rebecca G. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2007, 293 (06) :G1147-G1154
[10]   The bioartificial kidney: current status and future promise [J].
Humes, H. David ;
Buffington, Deborah ;
Westover, Angela J. ;
Roy, Shuvo ;
Fissell, William H. .
PEDIATRIC NEPHROLOGY, 2014, 29 (03) :343-351