A novel technique can jump-start the creation of blood vessels, researchers have reported in Nature Biotechnology.
The team used human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to create endothelial colony-forming cells (ECFCs).
These lab-generated ECFCs successfully produced human blood vessels in mice and restored blood flow to damaged retinas and limbs, without posing a risk of teratoma formation.
ECFCs can lose their ability to proliferate into new blood vessels as patients age or develop diseases such as peripheral arterial disease, said Mervin C. Yoder Jr, MD, of the Indiana University School of Medicine in Indianapolis.
He and his colleagues theorized that injecting patients with “younger,” more “enthusiastic” ECFCs might jump-start the process of creating new blood vessels. Such cells are difficult to find in adults but are common in umbilical cord blood.
With that in mind, the researchers developed a novel method to mature hiPSCs or hESCs into cells with the characteristics of ECFCs found in cord blood.
Both hiPSC-ECFCs and hESC-ECFCs exhibited properties of cord blood-derived ECFCs, including a homogenous monolayer with a cobblestone appearance and high clonal proliferative potential.
In addition, hiPSC-ECFCs and hESC-ECFCs formed capillary structures when cultured on Matrigel, and they generated in vivo inosculated vessels when implanted in immune-deficient mice.
In other murine experiments, hiPSC-ECFCs contributed to vascular repair of experimentally induced ischemic limbs and injured retinas. The cells’ effects were similar to those observed with cord blood-derived ECFCs and superior to effects observed with endothelial cells isolated using other published protocols.
Furthermore, hiPSC-ECFCs did not transition to nonendothelial cells over prolonged culture, and they could expand to more than 1 trillion endothelial cells in less than 3 months.
“This is one of the first studies using induced pluripotent stem cells that has been able to produce new cells in clinically relevant numbers, enough to enable a clinical trial,” Dr Yoder said.
He added that one of the next steps for this research is reaching an agreement with a facility approved to produce cells for use in human testing.
