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Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli.

William Gee Chang1, Alessia Fornoni2, Gregory Tietjen3

  • 11 Department of Medicine and Section of Nephrology, Yale University School of Medicine , New Haven, Connecticut.

Tissue Engineering. Part A
|September 29, 2015
PubMed
Summary

Engineered microvessels successfully perfused rat glomeruli in vivo, enhancing their survival. However, structural integrity of glomeruli requires further investigation for successful kidney tissue engineering.

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Area of Science:

  • Regenerative Medicine
  • Vascular Biology
  • Nephrology

Background:

  • Kidney transplantation is the primary treatment for end-stage renal disease, but organ scarcity is a significant limitation.
  • Tissue engineering offers a promising alternative to address the organ shortage, but vascularization remains a major hurdle.
  • Previous work demonstrated that Bcl-2 engineered endothelial cells (ECs) form perfused microvessels in collagen gels.

Purpose of the Study:

  • To evaluate the potential of self-assembling microvessels to perfuse complex organ structures.
  • To assess the viability and structural integrity of glomeruli perfused by engineered microvessels.

Main Methods:

  • Rat glomeruli expressing green fluorescent protein were microdissected and embedded in collagen gels.
  • Bcl-2-transduced ECs (Bcl-2-ECs) were co-implanted with glomeruli in immunodeficient mice.
  • Perfusion was assessed using intravital rhodamine dextran injections.
  • Glomerular structure was analyzed using podocin staining and transmission electron microscopy.

Main Results:

  • Co-implantation with Bcl-2-ECs significantly enhanced the survival of rat glomeruli.
  • Intravital imaging confirmed perfusion of surviving glomeruli via Bcl-2-EC-derived microvessels.
  • While podocin staining was maintained, electron microscopy revealed endothelial swelling and podocyte foot process effacement.

Conclusions:

  • Self-assembled microvessels can connect with and perfuse glomerular capillaries, demonstrating proof of concept for vascularizing engineered kidney tissue.
  • Perfusion alone, while crucial for survival, may not be sufficient to maintain the normal ultrastructure of glomeruli.
  • Further research is needed to optimize conditions for maintaining glomerular structure and function in engineered constructs.