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Isogenic Kidney Glomerulus Chip Engineered from Human Induced Pluripotent Stem Cells
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CD133+ endothelial progenitor cells as a potential cell source for a bioartificial glomerulus.

Duc M Vu1, Haruchika Masuda, Tun A Yokoyama

  • 1Division of Nephrology and Metabolism, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.

Tissue Engineering. Part A
|April 11, 2009
PubMed
Summary

Human umbilical cord blood CD133(+) endothelial progenitor cells (EPCs) show promise for bioartificial glomerulus development. These cells exhibit endothelial cell features and enhance ultrafiltration, suggesting their potential application in hemofiltration technology.

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Isolation of Endothelial Progenitor Cells from Human Umbilical Cord Blood
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Area of Science:

  • Regenerative Medicine
  • Biomaterials Science
  • Vascular Biology

Background:

  • Development of bioartificial glomeruli requires endothelial cells that are expandable, nonimmunogenic, antithrombogenic, and highly permeable.
  • Human umbilical cord blood CD133(+) endothelial progenitor cells (EPCs) are a potential cell source for endothelializing hemofilters.

Purpose of the Study:

  • To evaluate the feasibility of using CD133(+) EPCs for the development of a bioartificial glomerulus.
  • To assess the endothelial characteristics, antithrombogenic properties, and ultrafiltration capacity of EPCs.

Main Methods:

  • Expansion culture of CD133(+) EPCs from human umbilical cord blood.
  • Characterization of adhered EPCs for endothelial markers (CD31, vWF, VE-cadherin), Ulex europeus agglutinin I staining, and acetylated LDL uptake.
  • Assessment of prostaglandin secretion and expression of key enzymes and proteins (PLA2, COX-1, COX-2, PGI2 synthase, tPA, TM).
  • Evaluation of thrombomodulin (TM) protein activity in activating protein C.
  • Scanning electron microscopy to analyze platelet adhesion and aggregation.
  • Assessment of ultrafiltration capacity after cytochalasin B treatment to induce fenestrae.

Main Results:

  • Expansion culture significantly increased the number of adhered EPCs (25-30 times).
  • Adhered EPCs displayed key endothelial cell features and secreted 6-keto-prostaglandin F(1alpha) similarly to HUVECs.
  • EPCs expressed mRNA for enzymes involved in prostaglandin synthesis and coagulation/fibrinolysis (COX-1, COX-2, tPA, TM).
  • TM protein in EPCs demonstrated functional protein C activation.
  • The EPC monolayer exhibited suppressed platelet adhesion and aggregation.
  • Cytochalasin B treatment enhanced fenestration and significantly increased ultrafiltration.

Conclusions:

  • CD133(+) EPCs possess essential endothelial characteristics and functional properties suitable for bioartificial glomerulus applications.
  • These cells demonstrate antithrombogenic potential and enhanced ultrafiltration capabilities after specific treatment.
  • The findings strongly suggest that CD133(+) EPCs are a viable candidate for the endothelialization of bioartificial glomeruli, paving the way for improved hemofiltration devices.