UF Scientists Discover Adult Human Blood Stem Cells Can Build Human Blood Vessels In Mice
GAINESVILLE, Fla. – University of Florida scientists have scored another first in a string of advances using stem cells, this time showing they can inject mice with adult stem cells from human blood and spur human blood vessels to grow in their eyes.
Ultimately the approach will help researchers develop safer, faster ways of testing stem cell-based therapies for many diseases in people, including sight-robbing retinal disorders and cancer, says Edward Scott, an associate professor of molecular genetics at the UF Shands Cancer Center and director of the Program in Stem Cell Biology at UF’s College of Medicine. The findings were published in the Sept. 11 online edition of the journal Blood.
“This approach makes it faster for us to test therapies, find which ones work and try to improve them, so we can get them to clinical trial status faster,” said Scott, whose research team last year discovered that mouse blood stem cells could form mouse blood vessels in mice. “Unfortunately, there have been a number of times where mice can do things but people can’t. We wanted to make sure that human cells can do these same things. Now we know that the things we’re studying in the mouse are going to be applicable in humans.”
Conducting initial studies in mice using their own cells and then following up on successes by substituting human cells in the animals provides scientists with a valuable safety check, Scott said, helping them verify preliminary findings and rule out potential roadblocks before launching studies in people.
“This now gives us a mouse model and a mouse-human model for looking at diabetic retinopathy and for being able to try things we just can’t do yet in people,” Scott said. “That gives us a lot more avenues to investigate.”
More than four decades ago, researchers were intrigued to learn a single blood stem cell taken from the bone marrow could restore the body’s entire blood system, maturing into its key components – red and white blood cells, and platelets.
The latest findings have caught the attention of doctors working to better treat or even prevent diseases characterized by excessive blood vessel growth, diseased arteries or other circulatory troubles. Eventually, an improved understanding of stem cells’ role in the development of these ailments could help physicians prompt new blood vessel growth when needed or block it when it feeds disease, Scott said.
“We now know a number of proteins and factors that are required to get the stem cell to make blood vessels,” Scott said. “Those give us targets to try to stop their activity and keep them from working, thereby preventing the vessels from forming. Now that we know where these repair cells come from, we have a lot of different things we can try now, and animal models to show whether or not they’re effective.”
In the current study, UF researchers transplanted human blood stem cells derived from umbilical cord blood into dozens of mice lacking an immune system, all models for the human eye condition known as retinopathy. This diabetes-related complication, the leading cause of adult blindness in the United States, is characterized by a degenerative process that injures existing blood vessels and triggers new capillaries to form as the body struggles to repair the light-sensing retina. These new capillaries actually foster additional damage.
Within four to six weeks, human blood vessels grew in the animals’ eyes. Scientists used staining techniques to differentiate between mouse cells and human ones.
“What this study is demonstrating is the remarkable ability of stem cells that are derived from blood to reconstitute tissues in other organs,” said Dr. John R. Wingard, a UF professor of medicine and associate director of clinical and translational research at the UF Shands Cancer Center. “We are gaining increasing information about the potential of these cells to restore function in brain, heart, liver and other tissues. The more we learn about this, the more horizons are expanding as to clinical applications. And that’s really what our interest is in providing cells for laboratory research – it’s to identify new clinical uses for stem cells in both cancers as well as in other human illnesses.”
UF researchers will next use their findings to test ways of preventing retinopathy in mice, and also to block blood vessel formation in solid tumors, using human pancreatic and human breast cancer cells.
“Once again we’ll be using the mouse-human system to confirm that what works in a mouse works on human cells before trying to take it to a clinical trial,” Scott said. “We’re excited about having both systems to work with, so at every step along the way we can confirm that things we find in mice hold true for humans.”
Scott added that a process called cell fusion – in which stem cells don’t mature into cells of another type but simply meld with them, taking on their appearance – didn’t factor into the findings. Last year he and his colleagues, writing in Nature Medicine, warned that some researchers who had reported discovering that stem cells had transformed into certain cell types, such as liver cells, might actually have witnessed cell fusion, not a true conversion from one cell type to another, known as transdifferentiation. So the UF researchers could safely say the blood stem cells they used truly grew into the cells that constitute blood vessels.
“We saw true stem cell plasticity,” Scott said. “As we’re trying to target therapies against stem cells against diseases associated with blood vessels, then we know they’re the right things to target, whereas if fusion is playing a role we’d potentially be targeting the wrong thing with our therapy.”