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2015 ; 21
(21-22
): 2673-9
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Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli
#MMPMID26414101
Chang WG
; Fornoni A
; Tietjen G
; Mendez JJ
; Niklason LE
; Saltzman WM
; Pober JS
Tissue Eng Part A
2015[Nov]; 21
(21-22
): 2673-9
PMID26414101
show ga
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.