Long lasting blood vessels created in mice using human stem cells

Washington, July 16 : Researchers at Massachusetts General Hospital (MGH) have used vascular precursor cells derived from human induced pluripotent stem cells (iPSCs) to generate, in mice, functional blood vessels that lasted as long as nine months.

In their report, the investigators describe using iPSCs - reprogrammed adult cells that have many of the characteristics of embryonic stem cells - from both healthy adults and from individuals with type 1 diabetes to generate blood vessels on the outer surface of the brain or under the skin of 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," Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and co-senior author of the study, said.

"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 said.

The ability to regenerate or repair blood vessels could make a crucial difference in the treatment of cardiovascular disease -- which continues to be the number one cause of death in the US -- and other conditions caused by blood vessel damage, such as the vascular complications of diabetes.

In addition, providing a vascular supply to newly-generated tissue remains one of the greatest barriers facing efforts to build solid organs through tissue engineering.

Several previous studies have generated from iPSCs the types of cells required to build blood vessels -- endothelial cells that line vessels and connective tissue cells that provide structural support -- but those cells could not form long-lasting vessels once introduced into animal models.

"The biggest challenge we faced during the early phase of this project was establishing a reliable protocol to generate endothelial cell lines that produced great quantities of precursor cells that could generate strong, durable blood vessels," co-senior author Dai Fukumura, MD, PhD, also of the Steele Lab, said.

The MGH team adapted a method originally used to derive endothelial cells from human embryonic stem cells (hESCs).

But while that method used a single protein marker to identify vascular progenitors, the researchers sorted out iPSC-derived cells that expressed not only that protein but also two other protein markers of vascular potential.

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Long lasting blood vessels created in mice using human stem cells