Adapting to the Coronavirus Pandemic: Building and Incorporating a Diagnostic Pipeline in a Shared Resource Laboratory.

In March 2020, with lockdown due to the coronavirus pandemic underway, the Francis Crick Institute (the Crick) regeared its research laboratories into clinical testing facilities. Two pipelines were established, one for polymerase chain reaction and the other for Serology. This article discusses the Cricks Flow Cytometry Science Technology Platform (Flow STP) role in setting up the Serology pipeline.

Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors.

Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs.

Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutations.

The efficacy of tyrosine kinase (TK) inhibitors on non-cycling acute myeloid leukaemia (AML) cells, previously shown to have potent tumourigenic potential, is unknown. This pilot study describes the first attempt to characterize non-cycling cells from a small series of human FMS-like tyrosine kinase 3 (FLT3) mutation positive samples. CD34+ AML cells from patients with FLT3 mutation positive AML were cultured on murine stroma.

The differentiation and engraftment potential of mouse hematopoietic stem cells is maintained after bio-electrospray.

The bio-electrospray technique has been recently pioneered to manipulate living, immortalised and primary cells, including a wide range of stem cells. Studies have demonstrated that the creation of viable, fully functional in vitro microenvironments is possible using this technique. By modifying the bio-electrospray procedure (referred to as cell electrospinning), a variety of microenvironment morphologies have been fabricated.

Clonal heterogeneity in growth kinetics of CD34+CD38- human cord blood cells in vitro is correlated with gene expression pattern and telomere length.

Human hematopoietic stem cells (HSCs) are characterized by an extensive proliferative capacity that decreases from fetal liver to cord blood (CB) to adult bone marrow. In previous studies, it was demonstrated that the proliferative capacity of individual CD34+CD38- HSC clones is correlated with their growth kinetics in vitro and that HSC turnover in vivo can be estimated by telomere-length measurements. The present study was aimed at the characterization of the clonal composition of CD34+CD38- human umbilical CB cells in terms of growth kinetics, telomere length, and gene expression profile.

CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin.

CUB-domain-containing protein 1 (CDCP1) is a novel transmembrane molecule that is expressed in metastatic colon and breast tumors as well as on the surface of hematopoietic stem cells. In this study, we used multiparameter flow cytometry and antibodies against CDCP1 to analyze the expression of CDCP1 on defined hematopoietic cell subsets of different sources. In addition, CDCP1 expression on leukemic blasts and on cells with nonhematopoietic stem/progenitor cell phenotypes was determined.

Inhibitory effect of imatinib on normal progenitor cells in vitro.

Imatinib is a novel tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive leukemias and other malignancies. Side effects are mostly moderate; however, a dose-dependent hematologic toxicity affecting all hematopoietic lineages is observed clinically. The aim of this study was to investigate the effect of imatinib on normal hematopoietic stem and progenitor cells in vitro.

Normalization of previously shortened telomere length under treatment with imatinib argues against a preexisting telomere length deficit in normal hematopoietic stem cells from patients with chronic myeloid leukemia.

Telomeres are composed of TTAGGG repeats and associated proteins. In somatic cells, telomere repeats are lost with each cell division, eventually leading to genetic instability and cellular senescence. In previous studies, we described substantial and disease stage-specific telomere shortening in peripheral blood (PB) leukocytes from patients with chronic myeloid leukemia (CML).