The development and maturation of megakaryocytes (MKs) is a complex and multistage cellular and biological process. The hematopoietic microenvironment plays an important role in megakaryocytopoiesis regulation. Stromal cells, an important ingredient in the hematopoietic microenvironment, may regulate the development of MKs via the adhesion with MKs and via augmentation of cytokine secretion. Our laboratory has previously isolated a novel population of stromal cells from human umbilical cord blood, called hUCBDSCs. Compared with hBMSCs, the hUCBDSCs express higher levels of stromal cell-derived factor-1 (SDF-1) and increase the colony-forming-unit-megakaryocytes (CFU-MK). Meanwhile, there are reports identified a migration defect in PECAM-1-deficient MKs in response to a gradient of SDF-1. Based on literature searches and our experimental findings, we present a hypothesis that hUCBDSCs, secreting high level of SDF-1, modulated the expression of PECAM-1 of MKs, to regulate the megakaryocyte development.