Mechanical regulation of cell migration and vessel dynamics directs capillaries to form large vascular trees
In the late 1800s, it was first proposed that changes in blood flow could direct the growth and development of blood vessels. In a new study, published in the journal Development, researchers at Baylor College of Medicine report that increases in blood flow induce small blood vessels called capillaries to fuse, increasing the size of the tube through which circulation moves and reducing resistance.
The researchers, led by Dr. Mary Dickinson, professor of molecular physiology and biophysics at BCM, used a special form of imaging called confocal microscopy to watch the vessels fuse together to accommodate increasing blood flow and then recruit endothelial cells to further enlarge the channel. This sets the stage for the vascular tree that enables blood to leave the heart and travel throughout the mature organism, said Dickinson, an expert in imaging such structures.
"It is one of the big hurdles in tissue engineering," said Dickinson. "We need to understand how these little structures get bigger and remodel to get the right blood flow to the right kind of tissue. These studies in the early mouse embryo may provide an important key."
Using confocal microscopy to track cell migrations in the blood vessels, she and her colleagues were able to track thousands of cells as vessels grew. When there is low flow, little happens, she said.
However, in environments where neighboring vessels are exposed to both low and high blood flow, or in vessels where it is high all the time, smaller vessels fuse to make bigger ones and endothelial cells are recruited to increase vessel size.
"It reduces resistance to blood flow by making the vessels bigger," she said. "They can deliver as much blood as possible and distribute the blood through the yolk sac efficiently."
"We are now trying to create engineered constructs that look like this vessel bed," she said. "As we try to recapitulate this natural activity, we are looking for the activating factor."
New confocal microscopes
New technology would make it easier, she said, and that technology is now available. Confocal microscopy is an optical imaging technique used to increase optical resolution and contrast of a micrograph by using point illumination and a spatial pinhole to eliminate out-of-focus light in specimens that are thicker than the focal plane.
New, higher sensitivity confocal microscopes now available in the Optical Imaging and Vital Microscopy facility can help with future research as well a light sheet microscope now on loan. Light sheet microscopy is a versatile imaging technique with that combines high imaging speed, crisper images with low levels of photobleaching and phototoxic effects that can harm specimens and reduce the quality of images.
Others who took part in this work include Drs. Ryan S. Udan and Tegy J. Vadakkan, also of the Department of Molecular Physiology and Biophysics at BCM.
Funding for this work came from the National Institutes of Health (R01 HL097520, R01 HL077187, K12 GM084897) and the American Heart Association (10POST4280097).