6 research outputs found
Correlation between HOXA7 and HOXA9 (A) and JAG2 and HLF (B) gene expression in human AML analyzed with TaqMan Low Density Array (TLDA).
<p>Spearman rank correlation analysis was done on the log ratio values obtained from the TLDA assay and calculated with the 2<sup>−ΔΔCT</sup> method (n = 34).</p
Genes changed by NA10 and ND13 but not by the ND13(N51S) mutant compared to the GFP control.
<p>Genes changed by NA10 and ND13 but not by the ND13(N51S) mutant compared to the GFP control.</p
Venn diagram of genes significantly activated (A) or repressed (B) in Sca1+, Lin- BM cells expressing the ND13, NA10 or ND13(N51S) mutant fusion genes compared to GFP control.
<p>Venn diagram of genes significantly activated (A) or repressed (B) in Sca1+, Lin- BM cells expressing the ND13, NA10 or ND13(N51S) mutant fusion genes compared to GFP control.</p
Gene expression levels in human AML relative to normal bone marrow.
<p>Gene expression levels in human AML relative to normal bone marrow.</p
Validation of microarray results with quantitative RT-PCR on unamplified RNA.
<p>Fold changes are calculated against an empty MIG control and <i>Gapdh</i> as endogenous control gene.</p
Small-Molecule Ice Recrystallization Inhibitors Improve the Post-Thaw Function of Hematopoietic Stem and Progenitor Cells
The success of hematopoietic
stem cell transplantation depends
in part on the number and the quality of cells transplanted. Cryoinjuries
during freezing and thawing reduce the ability of hematopoietic stem
and progenitor cells (HSPCs) to proliferate and differentiate after
thawing. Up to 20% of the patients undergoing umbilical cord blood
(UCB) transplant experience delayed or failed engraftment, likely
because of the inadequate hematopoietic potency of the unit. Therefore,
the optimization of cryopreservation protocols, with an emphasis on
the preservation of HSPCs, is an important issue. Current protocols
typically utilize a 10% dimethyl sulfoxide cryoprotectant solution.
This solution ensures 70–80% post-thaw cell viability by diluting
intracellular solutes and maintaining the cell volume during cryopreservation.
However, this solution fails to fully protect HSPCs, resulting in
the loss of potency. Therefore, a new class of cryoprotectants (<i>N</i>-aryl-d-aldonamides) was designed and assessed
for the ability to inhibit ice recrystallization and to protect HSPCs
against cryoinjury. Several highly active ice recrystallization inhibitors
were discovered. When used as additives to the conventional cryoprotectant
solution, these nontoxic small molecules improved the preservation
of functionally divergent hematopoietic progenitors in the colony-forming
unit and long-term culture-initiating cell assays. By contrast, structurally
similar compounds that did not inhibit ice recrystallization failed
to improve the post-thaw recovery of myeloid progenitors. Together,
these results demonstrate that the supplementation of cryopreservation
solution with compounds capable of controlling ice recrystallization
increases the post-thaw function and potency of HSPCs in UCB. This
increase may translate into reduced risk of engraftment failure and
allow for greater use of cryopreserved cord blood units