Generation of functional hemangioblasts from human embryonic stem cells

• Published in: Nature methods Vol. 4; no. 6; pp. 501 - 509
• Main Authors: Lanza, Robert, Lu, Shi-Jiang, Feng, Qiang, Caballero, Sergio, Chen, Yu, Moore, Malcolm A S, Grant, Maria B
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-06-2007
• Subjects: Animals; Blood circulation disorders; Blood Vessels - cytology; Care and treatment; Cell Differentiation; Diabetes Mellitus, Type 2; Diabetic Retinopathy - therapy; Embryonic stem cells; Embryonic Stem Cells - cytology; Hematopoietic Stem Cells - cytology; Hindlimb - blood supply; Humans; Injection; Ischemia - pathology; Ischemia - therapy; Methods; Mice; Mice, Inbred NOD; Mice, SCID; Mortality; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - therapy; Physiological aspects; Rats; Reperfusion Injury - therapy; Stem Cell Transplantation; Stem cells; Transgenic animals; Transplants & implants; United States
• ISSN: 1548-7091; 1548-7105
• DOI: 10.1038/nmeth1041

Recent evidence suggests the existence of progenitor cells in adult tissues that are capable of differentiating into vascular structures as well as into all hematopoietic cell lineages. Here we describe an efficient and reproducible method for generating large numbers of these bipotential progenitors-known as hemangioblasts-from human embryonic stem (hES) cells using an in vitro differentiation system. Blast cells expressed gene signatures characteristic of hemangioblasts, and could be expanded, cryopreserved and differentiated into multiple hematopoietic lineages as well as into endothelial cells. When we injected these cells into rats with diabetes or into mice with ischemia-reperfusion injury of the retina, they localized to the site of injury in the damaged vasculature and appeared to participate in repair. Injection of the cells also reduced the mortality rate after myocardial infarction and restored blood flow in hind limb ischemia in mouse models. Our data suggest that hES-derived blast cells (hES-BCs) could be important in vascular repair.