Growing new blood vessels when arteries are blocked
By Christopher Vaughan
June 21, 2023
Institute researchers have discovered that certain purified stem cell components of normal body fat, when combined in the right proportions and transplanted into the body, will grow into new blood vessels. The researchers showed that when the technique was used in mice it restored blood flow to areas where areas where arteries were blocked. The discovery may lead to effective new therapies that use people’s own fat to treat heart attacks and promote organ transplantation.
“Vascular disease is still a major cause of illness and death throughout the world, and currently we can only restore blood flow to existing arteries,” say institute member Charles Chan, PhD. “Our work shows promise that we might help the body generate large blood vessels, bypassing blocked or diseased arteries.” Chan, an assistant professor of Surgery, Patricia Nguyen, MD, an associate professor of Medicine, and Michael Longaker, MD, the Deane P. and Louise Mitchel Professor in the Stanford School of Medicine, are co-senior authors on the paper, which was published in the Journal of Arteriosclerosis, Thrombosis and Vascular Biology (ATVB). Institute member Irving Weissman, MD, was also involved in the research. Postdoctoral fellow Liming Zhao, MD, former Stanford PhD & MD student, Andrew Lee, and former Stanford bioinformatician, Koki Sasagawa, are co-first authors on the paper.
Scientists have known that the body can create small “collateral” arteries or capillaries in response ischemia (when the supply of blood and oxygen to tissue is cut off). However, the blood vessels that grow are too small and sparse to supply an ischemic organ. As a result, researchers have been unsuccessfully trying to identify the cells that give rise to these collateral arteries, in hopes of creating a more robust arterial growth. The collateral vessels seem to arise from so-called “mesenchymal” stem cells (MSC), which include a mix of different kinds of stem and progenitor cells for bone, fat, blood vessels and various other tissues.
The researchers used an array of advanced analytical techniques to narrow down exactly which cells in the mixed MSC population were actually responsible for growing the new arteries. They focused in on two populations that they call VSPC1 and VSPC2, but were confounded to find that neither of these pure populations gave rise to functional vessels. VSPC1 cells, when transplanted into animals, gave rise to stunted, incomplete blood vessels. VSPC2 cells gave rise to stunted vessels and fat. However, when the two populations were transplanted into mice together in a particular ratio, functional new blood vessels would arise.
“We found these two distinct cell populations have to be transplanted together to work because one kind of cell serves as the developmental niche that is required for the other cell to become a functional blood vessel,” Chan said. “Vessels start forming as soon as you transplant them.”
The discovery is clinically important because the treatment for a heart attack or other ischemic event might be found in the patient’s own fat, Chan says. “If someone has a heart attack, you first want to deal with the blockages, but then you want to encourage new artery growth,” Chan said. “In principle, doctors could potentially use liposuction to collect a patient’s fat, separate out these two cell populations, and transplant them back into heart tissue that has been deprived of oxygen,” Chan said.
“Fat is a readily available, abundant and renewable resource in America,” Longaker said. “It is promising to be able to use it to induce new blood vessels”
The technique could also be used for tissue transplants, Chan said. Currently, doctors performing tissue or organ transplants surgically connect only the major vessels, meaning that the tissue is not getting as much blood as it was before transplantation. “Surgeons could apply these two cell populations in a gel to the transplant area, and those cells would do the job of connecting the small vessels,” Chan said.
In addition, there is the possibility of using banked cells, collected from the fat of anyone who cared to donate. “Because these cells wouldn’t be immunologically matched to the patient, you would have to use anti-rejection drugs at first, but then you would gradually wean patients off the drugs as they regenerated their own vessels,” Chan said. “It’s like if a bridge is knocked out, these VSPC cells act like a pontoon bridge that you put up temporarily to keep supplies moving until you are able to repair the permanent bridge.”