Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS)

被引:20
作者
Johnston, Kimberly A. [1 ]
Westover, Angela J. [1 ]
Rojas-Pena, Alvaro [2 ]
Buffington, Deborah A. [1 ]
Pino, Christopher J. [1 ]
Smith, Peter L. [1 ]
Humes, H. David [1 ,3 ]
机构
[1] Innovat BioTherapies Inc, 650 Avis Rd,Suite 300, Ann Arbor, MI 48108 USA
[2] Univ Michigan, Ann Arbor Sect Transplantat Surg, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Ann Arbor Dept Internal Med Nephrol, Ann Arbor, MI 48109 USA
关键词
artificial kidney; kidney failure; end-stage renal disease; peritoneal dialysis; cell therapy; sheep model; TISSUE-ENGINEERED KIDNEY; UREMIC ANIMALS; SEPTIC SHOCK; DYSFUNCTION; THERAPY; FAILURE; DISEASE; REPLACEMENT; ACTIVATION; DIALYSIS;
D O I
10.1002/term.2206
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 x 10(8) renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright (c) 2016 John Wiley & Sons, Ltd.
引用
收藏
页码:3048 / 3055
页数:8
相关论文
共 29 条
[1]   The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing [J].
Anding, K ;
Gross, P ;
Rost, JM ;
Allgaier, D ;
Jacobs, E .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2003, 18 (10) :2067-2073
[2]   Wak Engineering Evolution [J].
Armignacco, Paolo ;
Garzotto, Francesco ;
Neri, Mauro ;
Lorenzin, Anna ;
Ronco, Claudio .
BLOOD PURIFICATION, 2015, 39 (1-3) :110-114
[3]   Immune cell dysfunction and inflammation in end-stage renal disease [J].
Betjes, Michiel G. H. .
NATURE REVIEWS NEPHROLOGY, 2013, 9 (05) :255-265
[4]   Bioartificial Renal Epithelial Cell System (BRECS): A Compact, Cryopreservable Extracorporeal Renal Replacement Device [J].
Buffington, Deborah A. ;
Pino, Christopher J. ;
Chen, Lijun ;
Westover, Angela J. ;
Hageman, Gretchen ;
Humes, H. David .
CELL MEDICINE, 2012, 4 (01) :33-43
[5]  
Clark JD, 1996, INT LAB ANIM RES J, V38, P41
[6]  
Davenport Andrew, 2012, Adv Perit Dial, V28, P97
[7]   Bioartificial kidney ameliorates Gram-negative bacteria-induced septic shock in uremic animals [J].
Fissell, WH ;
Lou, L ;
Abrishami, S ;
Buffington, DA ;
Humes, HD .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2003, 14 (02) :454-461
[8]  
HaagWeber M, 1996, SEMIN NEPHROL, V16, P192
[9]   Metabolic replacement of kidney function in uremic animals with a bioartificial kidney containing human cells [J].
Humes, HD ;
Fissell, WH ;
Weitzel, WF ;
Buffington, DA ;
Westover, AJ ;
MacKay, SM ;
Gutierrez, JM .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2002, 39 (05) :1078-1087
[10]   Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure [J].
Humes, HD ;
Weitzel, WF ;
Bartlett, RH ;
Swaniker, FC ;
Paganini, EP ;
Luderer, JR ;
Sobota, J .
KIDNEY INTERNATIONAL, 2004, 66 (04) :1578-1588