Nav: Home

Researchers find adult endothelial stem cells that can make fully functional blood vessels

February 15, 2018

Osaka - The proper function of blood vessels is essential to life: blood vessels are responsible for transporting oxygen-rich red blood cells, nutrients, and immune cells throughout the body, to name just a few functions. Defects in blood vessels can correspondingly lead to a variety of life-threatening diseases. Stem cells, which are undifferentiated cells that can generate new tissues, have significant potential in regenerative medicine and treating various disorders. In blood vessels, the existence of tissue-resident stem cells has been intensely debated. A research team centered at Osaka University may now have discovered the elusive stem cell, providing evidence for adult vascular endothelial stem cells (VESCs) capable of generating fully functional blood vessels.

The research team had previously identified a population of endothelial cells (ECs), isolated from the inner most layer of blood vessels, with properties resembling those of stem cells. The cells were actually isolated by functional analysis, so the team was interested in finding molecular markers that specifically define endothelial stem cells. The research was reported in Cell Stem Cell.

"Our approach was to look for a cell-surface protein that is highly expressed in the endothelial stem-like population, but not in other ECs," explains Nobuyuki Takakura, who led this study. "Once we found a clear stem marker of ECs, we could then sort the cells based on the proteins expressed on their surface. This would theoretically allow us to isolate a homogeneous pool of candidate endothelial stem cells."

The researchers found a highly abundant glycoprotein, called CD157, expressed in the small fraction of EC population. After isolating just the ECs that expressed CD157, they set out to determine whether they were truly VESCs. The key characteristic of stem cells is their ability to regenerate themselves, so they hypothesized that the CD157-positive ECs would be able to form new blood vessels. The team tested this idea by experimentally injuring mice, damaging the blood vessels that supply blood to the liver, and injecting them with CD157-positive ECs isolated from the liver.

"The results were more than we could have hoped for," Takakura adds. "A month after transplantation, the CD157-enriched cells generated fully functional portal veins, portal venules, sinusoids, hepatic venules, and arteries--essentially, every type of blood vessel found in a healthy liver. We were very encouraged by the result, so we followed up by injecting mice with just one cell each. The success rate was smaller, but even a single cell was enough to reconstitute their blood vessels."

In addition to repairing injured tissue, stem cells are crucial to maintaining healthy tissue. As further confirmation that they had discovered a VESC, the team used a fluorescent reporter to follow the fate of these cells in non-injured healthy mice. A year later, the cells continued to replenish normal blood vessel tissue in the liver-precisely what would be expected of functioning, native stem cells.

Following the successful liver repair experiments, the team sought to determine how versatile the cells might be in treating other blood vessel-related diseases. Hemophilia A, a rare bleeding disorder in which blood is unable to clot properly, is caused by a genetic mutation that prevents liver blood vessels from making clotting factor VIII (FVIII). When VESCs collected from healthy mice were injected into mice with hemophilia A, the cells began generating new liver blood vessels--and the level of FVIII in the blood shot up, from less than 1% of normal to over 60%.

Notably, the therapeutic potential of these cells does not appear to be limited to liver defects. The researchers also used VESCs from muscle tissue to treat limb ischemia in mice, where a lack of oxygenated blood can lead to tissue damage and foot necrosis. The study potentially represents a turning point in cell-based therapies for blood vessel disorders.

"Our findings show that CD157-positive vascular endothelial stem cells give rise to a hierarchy of cell types that can repair vascular injury and maintain the normal blood vessel architecture," Takakura says. "We believe these findings represent an entirely new way of thinking about how blood vessels are formed and, ultimately, how stem cells can be used to treat disorders related to blood vessel malfunction."
-end-
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.

Website: http://resou.osaka-u.ac.jp/en/top

Osaka University

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.

Related Stem Cells Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".