How to make new blood vessels for patients who need them? Researchers at the University of Indiana University School of Medicine have developed a new therapy for illnesses such as peripheral artery disease. Diseases such a peripheral artery disease can lead to skin problems, gangrene and sometimes amputation.
Our bodies have the ability to repair blood vessels and creating new ones, because of a cell type called “endothelial colony-forming cells.” Unfortunately, these cells tend to lose their ability to proliferate and form new blood vessels as patients age or develop diseases like peripheral arterial disease, according to Mervin C. Yoder Jr., M.D., who is the Richard and Pauline Klingler Professor of Pediatrics at IU and leader of the research team.
Physicians can prescribe drugs that improve blood flow to patients with peripheral artery disease, but if the blood vessels are reduced in number or function, the benefits from such drugs are minimal. A better treatment might be to introduce “younger,” more effective endothelial colony forming into the affected tissues. In this case, such a treatment would jump-start the creation of new blood vessels. Gathering such cells, however is rather difficult, since endothelial colony-forming cells are somewhat difficult to find in adults, especially in those with peripheral arterial disease. Fortunately, endothelial colony-forming cells are rather numerous in umbilical cord blood.
Yoder and his colleagues published their work in the journal Nature Biotechnology, and they have reported that they have developed a potential therapy by using patient-specific induced pluripotent stem cells (iPSCs). Induced pluripotent stem cells are pluripotent stem cells that are derived from normal adult cells by means of genetic engineering and cell culture techniques. Once an iPSC line has been derived from a patient, they can potentially be differentiated into any adult cells type, including endothelial colony-forming cells.
In this paper, Yoder and his research team developed a novel methodology to differentiate iPSCs into cells with the characteristics of the endothelial colony-forming cells that are found in umbilical cord blood. These laboratory-generated endothelial colony-forming cells were injected into mice, and they proliferated and generated human blood vessels that nicely restored blood flow to damaged tissues in mouse retinas and limbs
Another problem addressed in this paper was growing endothelial colony-forming cells from umbilical cord in culture so that they can achieve sufficient numbers for therapies. In this paper, Yoder and his team designed a cell culture system that was able to dramatically expand these iPSC-derived endothelial colony-forming cells in culture from one founding cell to 100 million new cells in a little less than three months.
“This is one of the first studies using induced pluripotent stem cells that has [sic] been able to produce new cells in clinically relevant numbers — enough to enable a clinical trial,” Dr. Yoder said. According to Yoder, the next steps will be to reach solidify an agreement with a facility approved to produce cells for use in human testing. Additionally, Yoder would like to treat more than just peripheral artery disease, since he and his colleagues are evaluating the potential uses of these cells to treat diseases of the eye and lungs that involve blood flow problems.