Wednesday, June 25, 2008

Stem Cell Rejuvenation: Overcoming the Impediments of Aging and Disease

As individuals age, their stem cell pools tend to shrink. Likewise in the presence of many diseases, stem cells are less readily available. Even worse, the tissue response to stem cell supplementation is less successful under conditions of aging or disease. Researchers at the University of Frankfurt and Harvard Medical School have discovered ways of replenishing stem cell pools in aging and disease, as well as means of pre-treating diseased tissues for more successful stem cell supplementation.
In addition to age, which is known to affect stem cells functions, risk factors for coronary artery disease (CAD) and heart failure diminish the capacity of the bone marrow–derived cell to contribute to functional repair (Figure 1). Although patients usually are exposed to more than one risk factor, the next paragraph will discuss the impact of the individual risk factors and disease entities on endogenous bone marrow–derived and circulating cells.

...Similar to the impaired function of circulating or bone marrow–derived cells by diabetes, other risk factors such as hypercholesterolemia26 and hypertension26,27 also were associated with reduced and dysfunctional circulating EPCs. In addition, circulating CD34+KDR+ or CD34+CD133+ KDR+CD45low cells were inversely correlated with smoking,7,28 and this reduction was reversed by smoking cessation.28

...In old rats, chronological age leads to telomeric shortening in CPCs, which by necessity generate a differentiated progeny that rapidly acquires the senescent phenotype.5 The daughter cells inherit the shortened telomeres of the maternal CPCs and, after a few rounds of division, express the senescence-associated protein p16INK4a. The pool of old cardiomyocytes progressively decreases and ventricular function is impaired. However, telomerase competent CPCs with long telomeres are present in the regions of storage in the atria and apex and these cells, after activation by growth factors, migrate to areas of damage where they create a population of young myocytes reversing to some extent the aging myopathy structurally and functionally. The senescent heart phenotype is partially corrected and the improvement in cardiac hemodynamics results in prolongation of maximum lifespan in the rat model.5 __Source__via__Ouroborus
The article goes on to discuss ways of pre-treating the stem cells to be injected to enhance survival, and ways of pre-treating the target tissue to improve homing, engraftment, survival, and differentiation.The researchers demonstrate that despite the handicaps acting against successful stem cell treatment in disease and aging, that specific therapeutic pre-treatments for the stem cells and the target tissue should be able to counteract these deficiencies, and allow successful stem cell treatment.

Much interesting and useful information at the linked--free access article.



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