Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System
Kidney microphysiological systems (MPS) serve as potentially valuable preclinical instruments in probing mechanisms of renal clearance and osmoregulation. Current kidney MPS models target regions of the nephron, such as the glomerulus and proximal tubule (PCT), but fail to incorporate multiple filtr...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Micromachines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-666X/12/8/983 |
| _version_ | 1797522847914000384 |
|---|---|
| author | Stephanie Y. Zhang Gretchen J. Mahler |
| author_facet | Stephanie Y. Zhang Gretchen J. Mahler |
| author_sort | Stephanie Y. Zhang |
| collection | DOAJ |
| description | Kidney microphysiological systems (MPS) serve as potentially valuable preclinical instruments in probing mechanisms of renal clearance and osmoregulation. Current kidney MPS models target regions of the nephron, such as the glomerulus and proximal tubule (PCT), but fail to incorporate multiple filtration and absorption interfaces. Here, we describe a novel, partially open glomerulus and PCT microdevice that integrates filtration and absorption in a single MPS. The system equalizes pressure on each side of the PCT that operates with one side “closed” by recirculating into the bloodstream, and the other “opened” by exiting as primary filtrate. This design precisely controls the internal fluid dynamics and prevents loss of all fluid to the open side. Through this feature, an in vitro human glomerulus and proximal tubule MPS was constructed to filter human serum albumin and reabsorb glucose for seven days of operation. For proof-of-concept experiments, three human-derived cell types—conditionally immortalized human podocytes (CIHP-1), human umbilical vein endothelial cells (HUVECs), and human proximal tubule cells (HK-2)—were adapted into a common serum-free medium prior to being seeded into the three-component MPS (T-junction splitter, glomerular housing unit, and parallel proximal tubule barrier model). This system was optimized geometrically (tubing length, tubing internal diameter, and inlet flow rate) using in silico computational modeling. The prototype tri-culture MPS successfully filtered blood serum protein and generated albumin filtration in a physiologically realistic manner, while the device cultured only with proximal tubule cells did not. This glomerulus and proximal convoluted tubule MPS is a potential prototype for the human kidney used in both human-relevant testing and examining pharmacokinetic interactions. |
| first_indexed | 2024-03-10T08:35:10Z |
| format | Article |
| id | doaj.art-68138dc8d78d41c69c16a455b36bb1a1 |
| institution | Directory Open Access Journal |
| issn | 2072-666X |
| language | English |
| last_indexed | 2024-03-10T08:35:10Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj.art-68138dc8d78d41c69c16a455b36bb1a12023-11-22T08:45:01ZengMDPI AGMicromachines2072-666X2021-08-0112898310.3390/mi12080983Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological SystemStephanie Y. Zhang0Gretchen J. Mahler1Department of Biomedical Engineering, The State University of New York at Binghamton, Binghamton, NY 13902, USADepartment of Biomedical Engineering, The State University of New York at Binghamton, Binghamton, NY 13902, USAKidney microphysiological systems (MPS) serve as potentially valuable preclinical instruments in probing mechanisms of renal clearance and osmoregulation. Current kidney MPS models target regions of the nephron, such as the glomerulus and proximal tubule (PCT), but fail to incorporate multiple filtration and absorption interfaces. Here, we describe a novel, partially open glomerulus and PCT microdevice that integrates filtration and absorption in a single MPS. The system equalizes pressure on each side of the PCT that operates with one side “closed” by recirculating into the bloodstream, and the other “opened” by exiting as primary filtrate. This design precisely controls the internal fluid dynamics and prevents loss of all fluid to the open side. Through this feature, an in vitro human glomerulus and proximal tubule MPS was constructed to filter human serum albumin and reabsorb glucose for seven days of operation. For proof-of-concept experiments, three human-derived cell types—conditionally immortalized human podocytes (CIHP-1), human umbilical vein endothelial cells (HUVECs), and human proximal tubule cells (HK-2)—were adapted into a common serum-free medium prior to being seeded into the three-component MPS (T-junction splitter, glomerular housing unit, and parallel proximal tubule barrier model). This system was optimized geometrically (tubing length, tubing internal diameter, and inlet flow rate) using in silico computational modeling. The prototype tri-culture MPS successfully filtered blood serum protein and generated albumin filtration in a physiologically realistic manner, while the device cultured only with proximal tubule cells did not. This glomerulus and proximal convoluted tubule MPS is a potential prototype for the human kidney used in both human-relevant testing and examining pharmacokinetic interactions.https://www.mdpi.com/2072-666X/12/8/983kidneycytoskeletonmicrofluidicscytotoxicitypharmacokinetics |
| spellingShingle | Stephanie Y. Zhang Gretchen J. Mahler Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System Micromachines kidney cytoskeleton microfluidics cytotoxicity pharmacokinetics |
| title | Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System |
| title_full | Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System |
| title_fullStr | Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System |
| title_full_unstemmed | Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System |
| title_short | Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System |
| title_sort | modelling renal filtration and reabsorption processes in a human glomerulus and proximal tubule microphysiological system |
| topic | kidney cytoskeleton microfluidics cytotoxicity pharmacokinetics |
| url | https://www.mdpi.com/2072-666X/12/8/983 |
| work_keys_str_mv | AT stephanieyzhang modellingrenalfiltrationandreabsorptionprocessesinahumanglomerulusandproximaltubulemicrophysiologicalsystem AT gretchenjmahler modellingrenalfiltrationandreabsorptionprocessesinahumanglomerulusandproximaltubulemicrophysiologicalsystem |