Ageing of hematopoietic stem cells in human

by Alexey Bersenev on December 5, 2009 · 0 comments

in aging

 
It was proposed that decline in adult (tissue) stem cell number and function restricts longevity. But if we look at the hematopoietic system, decline in stem cell number with age is not the case.

A few interesting phenomenons of aged hematopoietic system were described in the literature:

    * number of hematopoietic stem cells (HSC) increases with age, but it’s strain-dependent;
    * function of HSC on single cell level decreases with age;
    * HSC homing ability declines with age;
    * lineage skewing in favor of myeloid lineages

Margaret Goodell’s group studied ageing of HSC in mice and concluded:

…we show here that in WT mice, stem cells decline in function, when measured per HSC, with a concomitant increase in their number, resulting in a minimal net change in overall HSC activity, strongly suggesting that stem cells are not likely to be a factor limiting hematopoietic regeneration with age.

But can we draw the parallels with human aged HSC? First of all I’d like to highlight why is it important to study ageing HSC in human.

Some observations of aged hematopoietic system in human:

    * decline in immune system function with age;
    * increased incidences of anemia, myelogenous leukemias and myelodisplastic syndrome with age;
    * increased donor age in bone marrow transplant correlates with higher transplant-related mortality and worse outcome;
    * old age is associate with poorer HSC mobilization compared with young donors.

So if we figure out what’s going on with hematopoiesis on HSC level with age, we can efficiently prevent and treat some pathological conditions associated with it. Also we can optimize bone marrow transplantation settings in old patients.

It turns out that we almost don’t have any studies which are done on HSC levels in human. In most studies total CD34+ progenitor population was sorted for genetic analysis or in vitro assays. Also function of aged human HSC was not assessed in transplantation assays.

But recently we got something. I’d like to share with you some unpublished data from a Stanford University group which will be presented at the annual ASH meeting this weekend. Overall their findings were the following:

    * immunophenotypic frequency of HSC (Lin-/CD34+/CD38-/CD90+) in elderly adult samples was 2-3 times more than in young adults;
    * quiescence of human HSC decreases with age;
    * myelo-erythroid differentiation capacity of aged HSC was normal, but B-lymphoid – was impaired in in vitro assay.

In aged individuals, HSC are more numerous and, as a population, are more myeloid biased than young HSC, which are more balanced in lymphoid and myeloid potential. We are currently investigating the causes of and mechanisms behind these highly specific age-associated changes in human HSC.

So, we can draw some parallels with mice, but we need to investigate the function of human HSC in transplantation assays.

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