Human CD34+ cells are capable of generating normal and JAK2V617F positive endothelial like cells in vivo

Abstract

Endothelial like cells (ELCs) are thought to originate from either a hierarchy of endothelial progenitor cells (EPC), monocytes or monocyte derived multipotent progenitor cells (MOMCs). In this report, the ability of CD34(+) cells to generate ELC in vivo was examined using an immunodeficient mouse transplant assay system. The Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms (MPN) are associated with the acquired mutation, JAK2V617F. In order to further examine the ability of cord blood and JAK2V617F positive MPN CD34(+) cells to generate ELC, CD34(+) cells were transplanted into NOD/SCID mice. Cells within the livers and lungs of recipient mice had phenotypic and molecular properties of human ELC as examined using RT-PCR, flow cytometric analysis and fluorescence microscopy. These cells possessed either human wild type JAK2 or JAK2V617F indicating that they were derived from the transplanted human cells and that a fraction of such cells were involved by the malignant process. Furthermore, human CD144(+) cells isolated from the livers of recipient mice formed clusters in vitro composed of ELC, which contained either wild type JAK2 or JAK2V617F suggesting that these cells are derived from either MOMC or EPC that have an extensive proliferative capacity as well as some degree of self renewal capacity. These studies indicate that adult CD34(+) cells can be affected by JAK2V617F and that they can generate ELC which might play a role in the development of thrombosis in patients with MPN.