An Approach to Reversing Aspects of Aging in the Blood Stem Cell Niche

Stem cell activity declines with age, and for at least some types of stem cell this is as much a matter of signaling and environment changes as is is a matter of accumulated molecular damage to the stem cell lineages themselves. Stem cells reside within a niche of supporting cells, and it is damage and change within that niche that is responsible to some degree for loss of stem cell activity, and thus progressive failure of the tissues maintained by those stem cells. This is a potential target for therapy: researchers here make an attempt to force a more youthful pattern of cell signaling onto the bone marrow niche within which hematopoietic stem cells reside, those responsible for generating blood and immune cells. This fails to address the underlying cellular damage that causes change, but appears to be capable of producing some benefits.

As people get older so do the hematopoietic stem cells (HSCs) that form their blood. In a new study, scientists propose rejuvenating the bone marrow niche where HSCs are created. This could mean younger acting HSCs that form healthier blood cells, boosted immunity in older people, and a better defense mechanism against certain cancers. The researchers conducted a number of experiments to test the formation and vitality of cells in and near the bone marrow microenvironment. One test in aging mice looked at the formation of endosteum stroma cells, which form a thin layer of connective tissue on the inner surface of bones. Another experiment monitored levels of osteopontin and other proteins linked to distinct cells in bone marrow during the aging process. Study authors say they observed reduced production of osteoblasts and other stroma cells in the endosteum of older mice. They also saw decreased osteopontin protein levels in the bone marrow of older animals, which they note was associated with reduced vigor and function of blood-forming HSCs.

Scientists followed up the earlier experiments by transplanting bone marrow cells from older mice (19-21 months) into young mice (8 to 10 weeks). In two other experiments, the authors also transplanted aged HSCs from older mice into younger mice, and they treated aged HSCs with a recombinant form of the osteopontin protein. Transplantation into the younger animals caused cells to act in a younger more vital manner, the authors report. This includes the presence of smaller numbers of HSCs with greater potential for forming different types of blood cells, which included larger populations of B and T cells and smaller production of myeloid cells.

The authors also saw aged HSCs treated with recombinant osteopontin regain their youthful characteristics and capacity to form different blood-cell types. Also observed was diminished signaling of the protein Cdc42, a protein previously shown to cause HSCs to age. Osteopontin levels are not only low in the bone marrow niche, but also in the blood upon aging. As a follow up to the current study, the researchers are investigating the possibility to use osteopontin replacement therapy in mice to counter the influence of an aging niche directly in the animals.

Link: https://www.cincinnatichildrens.org/news/release/2017/bone-marrow-stem-cell

Comments

As HSCs give rise to all blood and immune cell types it could potentially help reboot the immune system. This was something we were looking at doing at MMTP and it is good to see others are already doing this. This could lead to some level of immune system improvement in the old but also preventatively.

Posted by: Steve Hill at March 2nd, 2017 10:08 AM

To clarify we wanted to replace the HSCs completely not using signalling factors to improve aged cells but replacing them entirely. This could be considered a lesser version of this perhaps.

Posted by: Steve Hill at March 2nd, 2017 10:10 AM

Some interesting Information at the end of the article:
This work was funded by the DFG and BMBF (Federal Ministry of Education and Research) which are the two major funding bodies for state funded research in Germany. The BMBF even has a project named SyStaR for the loss of stem cell function in aged tissue.
https://www.uni-ulm.de/fileadmin/website_uni_ulm/iui.systar/downloads/SyStaR_Brosch%C3%BCre.pdf
I couldn't find the numbers but BMBF projects are typically in the same ballpark as the SENS budget and can easily get bigger with EU funding if they produce appropriate results.

Posted by: Matthias F at March 2nd, 2017 11:33 AM

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