When embedded in collagenous gel and implanted into animal tissue, endothelial cells can form networks and integrate with the host vasculature. Although this system has great potential for clinical applications, it is not yet sufficiently robust. A major reason for this is failure of the engrafted cells to connect with the host blood vessels through anastomosis, and very little is known about this process. Using longitudinal intravital imaging, we identified the mechanism responsible for the connections, and determined the rate-limiting step that slows the perfusion. The mechanism of vessel anastomosis involves wrapping of existing vessels by the engrafted cells, disruption of the host vessel wall and endothelial junction reassignment. The process allows the nascent vessels to "tap" into the pre-existing network. The proposed project will accelerate this process by specifically targeting components that hinder tapping, including basement membrane (Aim 1), host pericytes (Aim 2) and host endothelium (Aim 3).

Public Health Relevance

Although it's an essential step for survival of transplanted or engineered tissue, very little is known about how blood vessel networks in the graft connect with host vessels to achieve perfusion. By observing the formation of these connections using intravital imaging, we found that the implanted vessels connect by wrapping around host vessels and degrading them to steal the blood flow. In the proposed work we will take advantage of our knowledge of this process to accelerate perfusion of grafts.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL106584-02
Application #
8440749
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Lundberg, Martha
Project Start
2012-03-08
Project End
2016-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
2
Fiscal Year
2013
Total Cost
$329,080
Indirect Cost
$138,680
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Kesler, Cristina T; Liao, Shan; Munn, Lance L et al. (2013) Lymphatic vessels in health and disease. Wiley Interdiscip Rev Syst Biol Med 5:111-24