Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells

Abstract

During early embryogenesis, blood vessels and hematopoietic cells arise from a common precursor cell, the hemangio-blast. Recent studies have identified endo-thelial progenitor cells in the peripheral blood, and there is accumulating evidence that a subset of these cells is derived from precursors in the bone marrow. Here we show that adult bone marrow derived , phenotypically defined he-matopoietic stem cells (c-kit , Sca-1 , lineage) give rise to functional endothe-lial cells. With the exception of the brain, donor-derived cells are rapidly integrated into blood vessels. Durably engrafted en-dothelial cells express CD31, produce von Willebrand factor, and take up low-density lipoprotein. Analysis of DNA content indicates that donor-derived endothe-lial cells are not the products of cell fusion. Self-renewal of stem cells with hematopoietic and endothelial cell potential was revealed by serial transplantation studies. The clonal origin of both hema-topoietic and endothelial cell outcomes was established by the transfer of a single cell. These results suggest that adult bone marrow-derived hematopoi-etic stem cells may serve as a reservoir for endothelial cell progenitors. (Blood.

Epigenetics and the plasticity of differentiation in normal and cancer stem cells

“…Under certain conditions, especially after tissue injury, adult hematopoietic stem cells can differentiate to cells of neural lineage (Eglitis and Mezey, 1997;Sigurjonsson et al, 2005), liver (Alison et al, 2000;Lagasse et al, 2000;Theise et al, 2000;Krause et al, 2001;Jang et al, 2004), muscle (Camargo et al, 2003;Corbel et al, 2003), skin (Krause et al, 2001) and endothelium (Orlic et al, 2001;Bailey et al, 2004) and can thus contribute to regeneration of these tissues when they are damaged. Mesenchymal stem cells in the bone marrow can differentiate to muscle (Ferrari et al, 1998;Dezawa et al, 2005), neural lineage cells (Kopen et al, 1999;Dezawa et al, 2004) and to various other cell types (Jiang et al, 2002).…”

Hepatic Targeting of Transplanted Liver Sinusoidal Endothelial Cells in Intact Mice *

“…7,18 Moreover, hepatic endothelial damage is associated with conditions, such as sepsis, impaired liver function, veno-occlusive disease, and graft versus host disease, that could potentially benefit from endothelial reconstitution. [22][23][24][25] In principle, transplanted LSEC could enter the liver through the systemic or portal circulation, because hepatic sinusoids receive blood from both the portal vein (70%) and the hepatic artery (30%).…”

“…[12][13][14][15][16] Stem cells capable of generating EC are of considerable interest in defining mechanisms in lineage advancement and in cell therapy. 17,18 Studies using hematopoietic, mesenchymal, and epithelial cells indicate that analysis of cell engraftment and function is necessary to establish the fate of transplanted cells. [19][20][21] This process involves cell targeting in specific organs (e.g., to establish suitable routes of cell administration or to assess cell trafficking in individual organs).…”

Long‐term persistence of host cells detected by X‐chromosome gene‐based assay in patients undergoing gender‐mismatched hematopoietic stem cell transplantation

“…The two main cellular components of bone marrow are hematopoietic cells and stromal cells, the latter including adipocytes, fibroblasts, endothelial cells, osteoblasts, and osteocytes. Using Y-chromosome FISH, Athamasou et al determined that, in BMT recipients, these stromal cells were host-derived [23], although a recent report suggests that donor-derived hematopoietic stem cells can give rise to functional endothelial cells at a later stage [26]. The former finding indicates that host stromal cells can survive conditioning regimens for HCT.…”