The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: December 9, 2011

hiPSC-derived HSCs Engraft Mouse Model

McMaster Stem Cell and Cancer Research Institute ♦ Published in Stem Cells, November 30, 2011

There are several sources currently being used to isolate hematopoietic stem cells (HSCs) for transplantation in humans. Included in these are the bone marrow, peripheral blood, and umbilical cord blood. However, HSCs derived from human embryonic stem cells (hESCs) have, as of yet, failed to be a viable source for transplantation. Although hESCs are capable of hematopoietic differentiation in the petri dish, their HSC progeny are unable to engraft human-mouse xenograft models. This investigation shows that human induced pluripotent stem cells (hiPSCs), which are also capable of hematopoietic differentiation in vitro, produce HSCs that can successfully engraft following transplantation into the mouse model; similar to HSCs from adult sources. This is an advance in terms of studying hematopoietic transplantation in humans from pluripotent sources. Despite the ability of hiPSC-derived HSCs to engraft they were unable to reconstitute hematopoiesis. However, they could establish colonies after being removed from the bone marrow compartment suggesting that a molecular mechanism blocks their capacity to differentiate in vivo. Investigators believe that misexpression of various microRNAs may explain why hiPSCs are unable to reconstitute hematopoiesis.

Breast Cancer Stem Cells, From Where Do They Originate?

British Columbia Cancer Agency ♦ University of Melbourne ♦ University of British Columbia

Published in Stem Cells, November 30, 2011

There has been a lot of talk recently about aldehyde dehydrogenase (ALDH) because it seems to be expressed across such a diversity of different stem cell types. We know that it is expressed by hematopoietic progenitors, mesenchymal progenitors, neural progenitors, and endothelial progenitors. Researchers investigating the expression of ALDH in a number of functionally defined mammary cell types have come across an interesting finding. They found that ALDH expression is actually lower in mammary stem/progenitor cells, that have bilineage differentiation potential, than it is in cells committed to particular lineages. Progenitor cells of the luminal lineage, for example, express relatively high levels of ALDH. It seems that a molecular switch upregulates ALDH, particularly the ALDH1A3 isoform, during the process of lineage commitment. The finding that ALDH is upregulated during differentiation challenges the notion that breast cancer stem cells arise from mammary stem cells. Recent reports have associated ALDH activity with breast cancer stem cells, but if ALDH expression is turned on during differentiation then breast cancer stem cells may in fact be the less primitive luminal progenitor. Further investigation of the temporal and spatial expression of ALDH in the breast should help explain this quandary.

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