Functional Vasculature Generated from Advanced Cell Technology’s Human Embryonic Stem Cells

Advanced Cell Technology, Inc. has reported that it is feasible to differentiate human embryonic stem cells (hESCs) into functional human vasculature.

The research, which appears in the January issue of the journal Regenerative Medicine, shows for the first time that human progenitor cells – known as hemangioblasts – have the potential for both endothelial cell (EC) and vascular smooth muscle cell (SMC) lineage differentiation. This dual potentiality is critical for the effective treatment of human vascular disease, especially the repair and formation of mature and larger-size (non-capillary) vessels.

“The cells participated in the formation of new blood vessels – both capillaries and larger vessels - and were capable of repairing damaged vessels in multiple vasculatures,” said Robert Lanza, M.D., Chief Scientific Officer at ACT, and senior author of the study.

“The cells restored blood flow in ischemic limbs to near normal levels. They also showed a similar regenerative capacity after myocardial infarction and participated in the repair of vascular injury in diabetic animals. The formation of mature and functional vasculature, except for capillary vessels, requires the interaction of endothelial and smooth muscle cells, the later playing a critical role in the structural and functional support of the vascular network. Thus, the ability to generate large numbers of these progenitor cells makes them an ideal source of cells for the treatment of human diseases caused by deficient vessel growth.”

Although endothelial cells play an essential role in vasculogenesis and angiogenesis and form capillary vasculatures, they alone cannot complete the process of vessel growth and development. Vascular smooth muscle cells play a critical role in the support of the vascular network by stabilizing nascent endothelial vessels during vascular development and blood vessel growth. This outer layer of cells also protects the fragile channels from rupture and helps control blood flow.

Until now there was no evidence that blast cells (hemangioblasts) or their equivalents generated from hESCs possessed the ability to differentiate into smooth muscle cells. ”The hESC-derived smooth muscle expressed SMC-specific markers (a-SM actin and calponin) and contracted upon stimulation with carbachol,” stated Shi-Jiang Lu, first author of the paper.

“When implanted in nude mice, the cells formed microvasculature with endothelial cells in Matrigel. The cells differentiated into both ECs and SMCs, and incorporated into blood vessels after injection into ischemic tissues, indicating that these cells are functional both in vitro and in vivo.”