Title:
UREMIC VASCULOPATHY MODEL USING ENDOTHELIAL CELLS DERIVED FROM INDUCED PLURIPOTENT STEM CELLS AND UREMIC COMPLEX, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/055083
Kind Code:
A1
Abstract:
The present invention relates to a model of uremic vasculopathy and uses of same. More specifically, the present invention relates to: a medium composition for producing an endothelial cell model of uremic vasculopathy, using a uremic complex that comprises urea and uric acid and may further comprise indoxyl sulfate, creatinine, or advanced glycation end products (AGEs); a preparation method for an endothelial cell model of uremic vasculopathy, comprising the step of treating endothelial cells with the uremic complex; an endothelial cell model of uremic vasculopathy, prepared by the preparation method; screening and toxicity testing methods, using the model, for agents that inhibit or treat uremic vasculopathy. The uremic complex comprising urea and uric acid of the present invention, merely by using said uremic toxins among other various kinds of uremic toxins, can enable creating a uremic environment in endothelial cells conveniently in a manner similar to when using the blood serum of a patient with chronic kidney disease. In addition, the uremic complex of the present invention, when used for preparing an endothelial cell model of uremic angiopathy, can produce an endothelial cell model capable of reflecting various symptoms of uremic angiopathy. Furthermore, by using endothelial cells differentiated from induced pluripotent stem cells when preparing the endothelial cell model of uremic vasculopathy, it is possible to produce an endothelial cell model of uremic vasculopathy with genetic characteristics reflected therein, which can be beneficially used in personalized drug screening for the treatment of patients with uremic vasculopathy, the development of new drugs, toxicity testing, and the like.
Inventors:
JANG HYE RYOUN (KR)
KIM YOON GOO (KR)
HUH WOO SEONG (KR)
KO JAE WOOK (KR)
KIM JUNG RYUL (KR)
KIM YOON GOO (KR)
HUH WOO SEONG (KR)
KO JAE WOOK (KR)
KIM JUNG RYUL (KR)
Application Number:
PCT/KR2019/011676
Publication Date:
March 19, 2020
Filing Date:
September 10, 2019
Export Citation:
Assignee:
SAMSUNG LIFE PUBLIC WELFARE FOUNDATION (KR)
International Classes:
G01N33/50; C12N5/071
Foreign References:
| KR20150058836A | 2015-05-29 |
Other References:
GUO, J. ET AL.: "Vasculopatliy in the setting of cardiorenal syndrome: Roles of protein-bound uremic toxins", AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, vol. 313, 21 April 2017 (2017-04-21), pages H1 - H13, XP055693188
HENAUT, L. ET AL.: "The impact of uremic toxins on vascular smooth muscle cell function", TOXINS, vol. 10, no. 218, 29 May 2018 (2018-05-29), pages 1 - 21, XP055693186
DOU, L. ET AL.: "P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines", KIDNEY INTERNATIONAL, vol. 62, 2002, pages 1999 - 2009, XP055693184
HUR, 1. ET AL.: "Serum uric acid and mortality risk among maintenance hemodialysis patients", KIDNEY RESEARCH AND CLINICAL PRACTICE, vol. 36, 2017, pages 302 - 304, XP055693182
HENAUT, L. ET AL.: "The impact of uremic toxins on vascular smooth muscle cell function", TOXINS, vol. 10, no. 218, 29 May 2018 (2018-05-29), pages 1 - 21, XP055693186
DOU, L. ET AL.: "P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines", KIDNEY INTERNATIONAL, vol. 62, 2002, pages 1999 - 2009, XP055693184
HUR, 1. ET AL.: "Serum uric acid and mortality risk among maintenance hemodialysis patients", KIDNEY RESEARCH AND CLINICAL PRACTICE, vol. 36, 2017, pages 302 - 304, XP055693182
Attorney, Agent or Firm:
KIM, Soon Woong (KR)
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