Aug, 2003
Bioengineered implantation of megalin-expressing cells: A potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
- Volume
- 14
- Number
- 8
- First page
- 2025
- Last page
- 2032
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1097/01.ASN.0000078804.98322.4A
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
Patients who have renal failure and are on dialysis therapy experience serious complications caused by low-molecular-weight uremic toxin proteins normally filtered by glomeruli and metabolized by proximal tubule cells (PTC). Dialysis-related amyloidosis is one such complication induced by systemic deposition of amyloid proteins derived from 12-kD beta(2)-microglobulin (beta(2)-M). Despite the use of high-flux membrane hemodialysis devices and direct absorbent columns, the removal of beta(2)-M is suboptimal, because the effects are transient and insufficient. Megalin is expressed in the apical membranes of PTC and recognized as a multiligand endocytic receptor that binds numerous low-molecular-weight proteins, including, beta(2)-M. This study tested the feasibility of an intra corporeal therapeutic model of continuous beta(2)-m removal using megalin-expressing cell implantation. By cell association and degradation assays, rat yolk sac-derived L2 cells were identified to internalize and degrade beta(2)-M via megalin. The cells were effectively implanted within the subcutaneous tissues of nude mice using a type I collagen scaffold and a method inducing local angiogenesis. After nephrectomy and intraperitoneal injection with I-125-beta(2)-m, it was found that the implanted cells took up the labeled ligand, efficiently removing it from the blood. Bioengineered implantation of megalin-expressing cells may represent a new supportive therapy for dialysis patients to compensate for the loss of renal protein metabolism and remove uremic toxin proteins.
- Link information
- ID information
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- DOI : 10.1097/01.ASN.0000078804.98322.4A
- ISSN : 1046-6673
- Pubmed ID : 12874456
- Web of Science ID : WOS:000184352600008