Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli

William Gee Chang, Alessia Fornoni, Gregory Tietjen, Julio J. Mendez, Laura E. Niklason, W. Mark Saltzman, Jordan S. Pober

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2673-2679
Number of pages7
JournalTissue Engineering - Part A
Volume21
Issue number21-22
DOIs
StatePublished - Nov 1 2015

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Endothelial cells
Microvessels
Endothelial Cells
Tissue
Kidney
Tissue Engineering
Collagen Type I
Tissue engineering
Collagen
Perfusion
Gels
Rats
Podocytes
Human Umbilical Vein Endothelial Cells
Proteins
Green Fluorescent Proteins
Transmission Electron Microscopy
Dextran
Kidney Transplantation
Chronic Kidney Failure

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Chang, W. G., Fornoni, A., Tietjen, G., Mendez, J. J., Niklason, L. E., Saltzman, W. M., & Pober, J. S. (2015). Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. Tissue Engineering - Part A, 21(21-22), 2673-2679. https://doi.org/10.1089/ten.tea.2015.0060

Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. / Chang, William Gee; Fornoni, Alessia; Tietjen, Gregory; Mendez, Julio J.; Niklason, Laura E.; Saltzman, W. Mark; Pober, Jordan S.

In: Tissue Engineering - Part A, Vol. 21, No. 21-22, 01.11.2015, p. 2673-2679.

Research output: Contribution to journalArticle

Chang, WG, Fornoni, A, Tietjen, G, Mendez, JJ, Niklason, LE, Saltzman, WM & Pober, JS 2015, 'Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli', Tissue Engineering - Part A, vol. 21, no. 21-22, pp. 2673-2679. https://doi.org/10.1089/ten.tea.2015.0060
Chang, William Gee ; Fornoni, Alessia ; Tietjen, Gregory ; Mendez, Julio J. ; Niklason, Laura E. ; Saltzman, W. Mark ; Pober, Jordan S. / Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. In: Tissue Engineering - Part A. 2015 ; Vol. 21, No. 21-22. pp. 2673-2679.
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