title: Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli.
abstract: Kidney transplantation is often the most effective therapy for end-stage renal disease, but there are not enough donor organs to meet the rising demand. Tissue engineering of kidneys is a potential solution to this organ shortage. Achieving microvascular perfusion has been a major barrier to engineering tissues beyond thin muscularized sheets such as the bladder wall. Our laboratory has previously reported that human umbilical vein endothelial cells (ECs) transduced with the antiapoptotic protein Bcl-2 will spontaneously organize into perfused microvessels within type I collagen gels when implanted in immunodeficient mice. To test if this system can be used to perfuse more complex structures, we combined Bcl-2-transduced ECs (Bcl-2-ECs) with renal glomeruli, the specialized vascular filtration units of the kidney. Microdissected green fluorescent protein-expressing rat glomeruli suspended in type I collagen gels were implanted within immunodeficient mice with or without the inclusion of Bcl-2-ECs. Survival of rat glomeruli was enhanced by coimplantation with Bcl-2-ECs. Intravital rhodamine dextran injections demonstrated that surviving glomeruli were perfused through Bcl-2-EC-derived microvessels. Perfused glomeruli maintained podocin staining, but transmission electron microscopy revealed endothelial swelling and podocyte foot process effacement. Anastomosis of microvessels derived from Bcl-2-ECs with glomerular capillaries provides proof of concept that self-assembled microvessels can perfuse specialized organ structures such as glomeruli, but that perfusion alone may be insufficient to maintain normal structure.
authors.affiliation: 1 Department of Medicine and Section of Nephrology, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: William Gee
authors.initials: WG
authors.lastname: Chang
authors.affiliation: 2 Division of Nephrology and Hypertension and Diabetes Research Institute, University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fornoni
authors.affiliation: 3 Department of Biomedical Engineering, Yale University , New Haven, Connecticut.
authors.forename: Gregory
authors.initials: G
authors.lastname: Tietjen
authors.affiliation: 4 Department of Anesthesiology, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Julio J
authors.initials: JJ
authors.lastname: Mendez
authors.affiliation: 4 Department of Anesthesiology, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
authors.affiliation: 3 Department of Biomedical Engineering, Yale University , New Haven, Connecticut.
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.affiliation: 5 Department of Immunobiology, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology / Q000601:surgery; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000166:cytology / Q000254:growth & development*; D051381:Rats; D055647:Rats, Transgenic; D015424:Reperfusion / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D014471:Umbilical Veins / Q000166:cytology