NATURE: 31. 10. 2013

NATURE: Arteriolar niches maintain haematopoietic stem cell quiescence

"Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)⁺ pericytes, distinct from sinusoid-associated leptin receptor (LEPR)⁺ cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2⁺ periarteriolar niches to LEPR⁺ perisinusoidal niches. Conditional depletion of NG2⁺ cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence."

http://www.nature.com/nature/journal/v502/n7473/full/nature12612.html

BLOOD: Prostaglandin-modulated umbilical cord blood hematopoietic stem cells transplantation

"Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E₂ (dmPGE₂) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE₂ could improve patient outcomes by increasing the “effective dose” of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a single UCB unit using dmPGE₂ before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE₂-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P = .045), coupled with preferential, long-term engraftment of the dmPGE₂-treated UCB unit in 10 of 12 treated participants."

http://bloodjournal.hematologylibrary.org/content/122/17/3074.abstract