Polyclonal regeneration of mouse bone marrow endothelial cells after irradiative conditioning.

Bone marrow endothelial cells (BM-ECs) are the essential components of the BM niche and support the function of hematopoietic stem cells (HSCs). However, conditioning for HSC transplantation causes damage to the recipients' BM-ECs and may lead to transplantation-related morbidity. Here, we investigated the cellular and clonal mechanisms of BM-EC regeneration after irradiative conditioning.

Resolving the hematopoietic stem cell state by linking functional and molecular assays.

One of the most challenging aspects of stem cell research is the reliance on retrospective assays for ascribing function. This is especially problematic for hematopoietic stem cell (HSC) research in which the current functional assay that formally establishes its HSC identity involves long-term serial transplantation assays that necessitate the destruction of the initial cell state many months before knowing that it was, in fact, an HSC. In combination with the explosion of equally destructive single-cell molecular assays, the paradox facing researchers is how to determine the molecular state of a functional HSC when you cannot concomitantly assess its functional and molecular properties.

The biology of hematopoietic stem cells and its clinical implications.

Hematopoietic stem cells (HSCs) give rise to all types of blood cells and self-renew their own population. The regeneration potential of HSCs has already been successfully translated into clinical applications. However, recent studies on the biology of HSCs may further extend their clinical use in future.

Role of Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia.

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene () expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(-413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility.

Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood.

Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes.