Blood Cells Reprogrammed into Blood Stem Cells

As researchers continue to work on cellular reprogramming, we will see an increasing number of new research results like this one. A compelling reason for this type of work is to secure low-cost and reliable sources of large numbers patient-matched cells, grown from easily obtained tissue samples such as skin and blood:

[Scientists] have reprogrammed mature blood cells from mice into blood-forming hematopoietic stem cells (HSCs), using a cocktail of eight genetic switches called transcription factors. The reprogrammed cells, which the researchers have dubbed induced HSCs (iHSCs), have the functional hallmarks of HSCs, are able to self-renew like HSCs, and can give rise to all of the cellular components of the blood like HSCs. The findings mark a significant step toward one of the most sought-after goals of regenerative medicine: the ability to produce HSCs suitable for hematopoietic stem cell transplantation (HSCT) from other cell types, in particular more mature or differentiated cells.

The success of any individual patient's HSCT is tied to the number of HSCs available for transplant: the more cells, the more likely the transplant will take hold. However, HSCs are quite rare. "HSCs only comprise about one in every 20,000 cells in the bone marrow. If we could generate autologous HSCs from a patient's other cells, it could be transformative for transplant medicine and for our ability to model diseases of blood development."

In a series of mouse transplantation experiments, [the team found that] Hlf, Runx1t1, Pbx1, Lmo2, Zfp37 and Prdm5, Mycn, and Meis1 were sufficient to robustly reprogram two kinds of blood progenitor cells (pro/pre B cells and common myeloid progenitor cells) into iHSCs. [The] team reprogrammed their source cells by exposing them to viruses containing the genes for all eight factors and a molecular switch that turned the factor genes on in the presence of doxycycline. They then transplanted the exposed cells into recipient mice and activated the genes by giving the mice doxycycline.

The resulting iHSCs were capable of generating the entire blood cell repertoire in the transplanted mice, showing that they had gained the ability to differentiate into all blood lineages. Stem cells collected from those recipients were themselves capable of reconstituting the blood of secondary transplant recipients, proving that the eight-factor cocktail could instill the capacity for self-renewal - a hallmark property of HSCs.



So if they can make these iHSCs in volume the bone marrow part of a bone marrow transplant will no longer be necessary.

I read that currently they currently destroy the patients immune system with chemo/radio therapy, then re-seed the bone marrow with the extracted HSCs. i'm wondering if there is an overlap between the SENS goal of reducing the memory T cell pool (without something so dangerous as chemo/radiotherapy) and developing a safer means of completely wiping out the immune system in bone marrow transplants.

Hopefully negating the bone marrow extraction part will lead to more research on destroying immune cells safely.

Posted by: Jim at April 25th, 2014 11:03 AM

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