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Abstract: TH-PO765

An In Vivo Vascularization Model for the Implantation of Embryonic Kidneys

Session Information

  • Bioengineering
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Hamon, Morgan, Greater Los Angeles Veterans Administration, Los Angeles, California, United States
  • Hauser, Peter V., Greater Los Angeles Veterans Administration, Los Angeles, California, United States
  • Zhao, Lifu, Sepulveda Research Corporation, North Hills, California, United States
  • Nishikawa, Masaki, GLAVAHS at Sepulveda, North Hills, California, United States
  • Kimura, Hiroshi, Tokai University, Hiratsuka, Japan
  • Yanagawa, Naomi, Sepulveda Research Corporation, North Hills, California, United States
  • Yanagawa, Norimoto, Greater Los Angeles Veterans Administration, Los Angeles, California, United States
Background

A major obstacle to implantation of ex vivo engineered 3D tissues is the incorporation of a functional vascular supply in order to minimize the ischemic injury and support the growth of the new tissue. This may be overcome in an in vivo vascularization model where the engineered tissues can be implanted into a pre-vascularized chamber. The main goal of our present study is to design such a vascularization chamber and test its applicability for the implantation of embryonic kidneys.

Methods

The chamber was composed of three polydimethylsiloxane (PDMS) layers: a base layer holding the chamber, a center layer containing the vascularization chamber with an opening on one side to allow the in-growth of blood vessels, and a top layer that closes the chamber. Pre-vascularization of the chamber was achieved by first loading the chamber with collagen I (C), matrigel (M) or matrigel+VEGF (MV), followed by implantation of the chamber between the abdominal aorta and vena cava in a mouse. After the chamber was pre-vascularized, mouse embryonic kidneys were placed onto the chamber. The growth and development of the embryonic kidneys were monitored and analyzed.

Results

We found that endothelial cells and developing vascular networks were detected in the chamber as early as 48h after implantation. Filling the chamber with MV significantly shortened the time required for pre-vascularizaion: 7 days for C loaded chambers, 5 days for M loaded chambers, and 2 days for MV loaded chambers. As compared to non-vascularized chambers, implantation of E12.5 mouse embryonic kidneys to pre-vascularized chambers showed significant increase in size and ureteric branching after 7 days.

Conclusion

We demonstrate in our present study that the in vivo vascularization model by using pre-vascularized chamber could be useful for the implantation of embryonic kidneys. Further studies are going on to optimize our system and examine the development and vascularization of the implanted embryonic kidneys.

Funding

  • Private Foundation Support