Adhesion receptor expression by CD34+ cells from peripheral blood or bone marrow grafts: correlation with time to engraftment.

Objective: This study was undertaken to define the pattern of cell adhesion receptor expression by the CD34+ progenitor cells from mobilized peripheral blood and bone marrow from normal and autologous donors, and to correlate the adhesion receptor profile with time to blood cell recovery for patients undergoing autologous transplant.

Methods: Blood cell recovery was determined by absolute neutrophil count (> 500/microL), time to last red cell transfusion, and platelet count (> 50,000/microL and > 100,000/microL). The analysis for expression of adhesion receptors alphaL (CD11a), alpha2 (CD49b), alpha3 (CD49c), alpha4 (CD49d), alpha5 (CD49e), alpha6 (CD49f), beta1 (CD29), L-selectin (CD62L), ICAM-1 (CD54), PECAM-1 (CD31), HCAM (CD44), and P-selectin (CD62P) was performed by two-color flow cytometry.

A specific heptapeptide from a phage display peptide library homes to bone marrow and binds to primitive hematopoietic stem cells.

Phage display peptide libraries have enabled the discovery of peptides that selectively target specific organs. Selection of organ-specific peptides is mediated through binding of peptides displayed on phage coat protein to adhesion molecules expressed within targeted organs. Hematopoietic stem cells selectively home to bone marrow, and certain adhesion receptors critical to this function have been demonstrated.

The molecular basis for the cytokine-induced defect in homing and engraftment of hematopoietic stem cells.

Objective: Hematopoietic stem cell homing and engraftment is dramatically altered by cytokine exposure. These studies address the molecular mechanisms responsible for the observed changes in transplantation biology.

Methods: Primitive murine hematopoietic stem cells were isolated by fluorescence-activated cell sorting of lineage depleted (Lin(-)) cells exhibiting low staining of Hoechst 33342 and rhodamine 123 dyes or Lin(-) cells bearing Sca.

Variables to predict engraftment of umbilical cord blood into immunodeficient mice: usefulness of the non-obese diabetic--severe combined immunodeficient assay.

Umbilical cord blood is an alternative stem cell source for patients without matched family donors. In this study, we examined several parameters that have not been studied in detail -- radiation dose, cell dose, age of mice, and maternal and neonatal characteristics of the cord blood donor -- that affect engraftment of cord blood in non-obese diabetic-severe combined immunodeficient (NOD--scid) mice. Engraftment, measured using flow cytometry analyses of human CD45(+) cells, was highest in 400 cGy-treated mice.

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.

Expression and function of colony-stimulating factors and their receptors in human prostate carcinoma cell lines.

Background: The predeliction for prostate carcinoma cells to metastasize to bone suggests the hypothesis that bone and/or bone marrow-derived factors may promote prostate carcinoma cell growth or survival, or serve as chemoattractants for these cells.

Methods: We screened three prostate carcinoma cell lines, DU-145, PC-3, and LNCaP, for the expression of several hematopoiesis-associated colony-stimulating factors (CSFs) and their receptors using RT-PCR (reverse transcriptase-polymerase chain reaction) and immunohistochemical methods, and examined their functional effects.

Results: All of these cell lines express granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), and the DU-145 and PC-3 lines express stem-cell factor (SCF), as determined by RT-PCR and ELISA.

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.

In an effort to investigate the role of creatine kinase and its substrates in malignancy we have tested the effect of cyclocreatine [1-carboxymethyl-2-iminoimidazolidine (CCr)] on the growth of tumor cells in vitro and in vivo. CCr is phosphorylated by creatine kinase to yield a synthetic phosphagen [(N-phosphorylcyclocreatine (CCr approximately P)] with thermodynamic and kinetic properties distinct from those of creatine phosphate. We show that CCr accumulates as CCr approximately P in tumor cells expressing a high level of creatine kinase, and that the accumulation of this phosphagen is detrimental to tumor cell growth.