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Stem cells are wasted on the young: The impact of aging on cell therapy… and potential solutions

Posted Jul 03 2008 4:12pm

One major barrier to the therapeutic use of pluripotent and totipotent cells is that by the time a patient needs them, their body has become less able to use them. The stem cell niche (i.e., those factors in the tissue microenvironment that stem cells require in order to function normally) changes with age, and not for the better: for example, embryonic stem cellslose proliferative capacitywhen confronted with aged niches.

This appears to be a general problem in metazoans, and is conserved between humans and relations as distant as arthropods — fortunately for us, because it means that the tools and genius of theDrosophilacommunity can be brought to bear on the problem. In the fruit fly, age-related changes in the stem cell niche are well-documented, especially in the reproductive system, and the molecular players are starting to be individually identified (see our previous post onDpp, this one onBMP,unpairedand cadherins, and this nicereviewof the whole story). There are one or two tissues in which stem cells actually becomemore numerouswith age, but the consensus seems to be that the aged microenvironment is generally not beneficial for stem cells. At least in the fly.

But what about species nearer and dearer to us? Fortunately, the human case is starting to be fleshed out in equally fine detail, and the state of the art has been thoroughly and artfully reviewed byStefanie Dimmeler and Annarosa Leri. (The article is open access, so the full text is available to everyone.) The authors focus on the heart but also address more general (and less tissue-specific) issues along the way:

Aging and Disease as Modifiers of Efficacy of Cell Therapy

Cell therapy is a promising option for treating ischemic diseases and heart failure. Adult stem and progenitor cells from various sources have experimentally been shown to augment the functional recovery after ischemia, and clinical trials have confirmed that autologous cell therapy using bone marrow—derived or circulating blood–derived progenitor cells is safe and provides beneficial effects. However, aging and risk factors for coronary artery disease affect the functional activity of the endogenous stem/progenitor cell pools, thereby at least partially limiting the therapeutic potential of the applied cells. In addition, age and disease affect the tissue environment, in which the cells are infused or injected. The present review article will summarize current evidence for cell impairment during aging and disease but also discuss novel approaches how to reverse the dysfunction of cells or to refresh the target tissue. Pretreatment of cells or the target tissue by small molecules, polymers, growth factors, or a combination thereof may provide useful approaches for enhancement of cell therapy for cardiovascular diseases.

The bad news about the impact of aging and disease factors on the prospects for cell therapy is tempered with good news — the final quarter of the piece is devoted to therapeutic strategies for overcoming the negative effects of the aged niche, with the ultimate goal of using stem cells even in suboptimal tissue microenvironments — i.e., in patients who need them.

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