Biomedical subjects

G Dooner

Publications and source records attributed to G Dooner.

3 recordsLinked to original sources

PubMed2005

The stem cell continuum: considerations on the heterogeneity and plasticity of marrow stem cells.

Traditional models of hematopoiesis have been hierarchical. Recent evidence showing that marrow stem cells are a cycling population and that the hematopoietic phenotype of these cells reversibly changes with cycle transit have suggested a continuum model of stem cell regulators. Studies on marrow cell conversion to lung cells have extended this continuum to cycle-related differentiation into nonhematopoietic stem cells. We postulate that stem cells transiting cell cycle continually change their chromatin structure, thus providing different windows of transcriptional opportunity and a continually changing phenotype. Final outcomes with this continuum model would be determined by the specific chromatin state of the cell and the presence of specific differentiation inducers.

Bone Marrow Cells↗

PubMed2005

The marrow cell continuum: stochastic determinism.

Traditional models of hematopoiesis have been hierarchical in nature. Over the past 10 years, we have developed data indicating that hematopoiesis is regulated in a continuum with deterministic and stochastic components. We have shown that the most primitive stem cells, as represented by lineage negative rhodamine(low) Hoechst(low) murine marrow cells are continuously or intermittently cycling as determined by in vivo BrdU labeling. When marrow stem cells are induced to transit cell cycle by in vitro exposure to cytokines, either IL-3, IL-6, IL-11, and steel factor or thrombopoietin, FLT3 ligand, and steel factor, they progress through cycle in a highly synchronized fashion. We have determined that when the stem cells progress through a cytokine stimulated cell cycle the homing, engraftment, adhesion protein, global gene expression, and hematopoietic differentiation phenotypes all change in a reversible fashion. This has led to the continuum model, in which, with cycle transit, chromatin is continually changing altering open transcription areas and providing a continually changing landscape of transcriptional opportunity. More recently, we have extended the changing differentiation profiles to differentiation into lung cells and found that non-hematopoietic differentiation also shows cycle related reversibly modulation. These observations all together support a continuum model of stem cell regulation in which the phenotype of the marrow stem cells is continually and reversibly changing over time.

Animals↗

PubMed2000

Effect of ex vivo cytokine treatment on human cord blood engraftment in NOD-scid mice.

Umbilical cord blood transplantation is considered an alternative to traditional bone marrow transplantation for patients who do not have matched sibling donors. In this study, we examined the effects of ex vivo treatment of human cord blood cells with cytokine mixtures and assessed the ability of treated cells to engraft in NOD-scid mice. We incubated the cord blood with a four-factor cytokine mixture of interleukin (IL)-3, IL-6, IL-11 and stem cell factor, or with a two-factor cytokine mixture of thrombopoietin and flt-3. Incubation of cord blood for 48 h with either cytokine mixture did not affect progenitor cell number or proliferative potential as measured by the high proliferative potential (HPP) assay. Cytokine-treated cord blood injected into irradiated NOD-scid mice resulted in multilineage human engraftment. Overall, incubation with cytokines resulted in variable levels of engraftment with different cord blood samples. Incubation of cord blood with the four-factor cytokine mixture resulted in increased survival of irradiated NOD-scid recipients. These results demonstrate that short-term ex vivo treatment of human progenitor cells gives variable results on in vivo multipotential capabilities.

Animals↗