The present invention relates to the generation of vascularized
human heart tissue from human primordial
Islet1-positive (ISL1+) progenitors, and more particularly the generation of vascularized
human heart tissue from human primordial
Islet1+ cardiovascular stem cells which are positive for markers ISL1+ / NKX2.5− / KDR−. One aspect of the invention relates to isolation of human ISL1+ primordial cells from human pluripotent cells, such as human ES cells or other human pluripotent
stem cell sources, wherein the human ISL1+ primordial cells can differentiate into three different lineages; cardiomyocyte lineages, endothelial lineages and
smooth muscle lineages. Another aspect relates to use and implantation of the human primordial ISL1+ progenitors into an
animal model to generate human vascularized heart tissue, and more particularly, the production of an
in vivo humanized model of
vascular disease. One embodiment relates to the use of an
in vivo humanized model of
vascular disease as an
assay, for example to assess
drug toxicity and / or identify agents which increase and decrease coronary
blood flow to the human vascularized heart tissue. Another embodiment relates to the therapeutic use of human primordial ISL1+ progenitors, for example, in one embodiment the invention provides methods for the treatment cardiovascular disorders and / or congenital
heart disease in a subject comprising
transplanting into subjects vascularized
human heart tissue generated from human ISL1+ progenitors.