July 16, 2013
Adult Human Cells Used To Create Long-Lived Blood Vessels
redOrbit Staff & Wire Reports - Your Universe Online
Massachusetts General Hospital (MGH) researchers have managed to create long-lasting blood vessels from reprogrammed human induced pluripotent stem cells (iPSCs), This groundbreaking research is published in the latest issue of the Proceedings of the National Academy of Sciences (PNAS) Early Edition.
Using vascular precursor cells derived from iPSCs, reprogrammed adult cells that have several of the same characteristics of embryonic stem cells, the scientists were able to create functional blood vessels in an animal model that lasted up to nine months. In their study, the authors describe how they used cells from both healthy adults and those with type 1 diabetes to generate blood vessels under the skin or on the brain's outer surface in mice.
"The discovery of ways to bring mature cells back to a 'stem-like' state that can differentiate into many different types of tissue has brought enormous potential to the field of cell-based regenerative medicine, but the challenge of deriving functional cells from these iPSCs still remains," said co-author Rakesh Jain, director of the MGH Steele Laboratory for Tumor Biology.
"Our team has developed an efficient method to generate vascular precursor cells from human iPSCs and used them to create networks of engineered blood vessels in living mice," he added.
Their work could lead to medical advances such as the treatment of cardiovascular disease and other ailments through the regeneration or repair of blood vessels, and could eliminate one of the obstacles preventing tissue engineering from creating usable organs.
Researchers have, in the past, been able to use iPSCs to build endothelial cells that line vessels and connective tissue cells that provide structural support. However, those cells were unable to form long-lasting blood vessels once they were introduced into animal models.
According to co-senior author Dai Fukumura, also of the Steele Lab, the largest obstacle the researchers faced was, "establishing a reliable protocol to generate endothelial cell lines that produced great quantities of precursor cells that could generate strong, durable blood vessels."
Jain, Fukumura and their colleagues took a method originally used to derive endothelial cells from human embryonic stem cells (hESCs) and adapted it. The method originally used a single protein marker to identify vascular progenitors, but the iPSC-derived cells used that protein marker as well as two others with vascular potential.
Next, they expanded that population using a culture system that members of the team developed to differentiate endothelial cells from hESCs, and found only iPSC-derived cells expressing all three markers were capable of generating endothelial cells with the full potential of forming functional blood vessels.
"To test the capacity of those cells to generate functional blood vessels, they implanted onto the surface of the brains of mice a combination of the iPSC-derived endothelial precursor cells expressing the three markers with the mesenchymal precursors that generate essential structural cells," the hospital explained in a statement. "Within two weeks, the implanted cells had formed networks of blood-perfused vessels that appeared to function as well as adjacent natural vessels and continued to function for as long as 280 days in the living animals.
"While implantation of the combined precursor populations under the skin of the animals also generated functional blood vessels, it required implantation of five times more cells, and the vessels were short-lived, an observation consistent with the team's previous studies of vessel generation in these two locations," they added.
Since type 1 diabetes can damage a person's blood vessels, and those patients could benefit from the ability to manufacture blood vessels, the study authors wanted to figure out if iPSCs derived from their cells could help generate functional blood vessels.
"As with cells from healthy individuals, precursors derived from T1D-iPSCs were able to generate functional, long-lasting blood vessels," the hospital said. "However, the researchers note, different lines of the T1D-iPSCs -- including different lines derived from the same patient -- showed differences in cell-generating potential, indicating the need to better understand the underlying mechanisms."
"The potential applications of iPSC-generated blood vessels are broad -- from repairing damaged vessels supplying the heart or brain to preventing the need to amputate limbs because of the vascular complication of diabetes,â noted co-lead author Rekha Samuel of the Christian Medical College in India.
However, she cautions scientists must first overcome challenges such as, "the variability of iPSC lines and the long-term safety issues involved in the use of these cells," as well as develop, "better ways of engineering the specific type of endothelial cell needed for specific organs and functions."