Physiological Changes: Stem Cells

Mesenchymal stem cells are in bone marrow, are associated with blood vessels, are present in the connective tissue of muscle, and are in a number of anatomical locations. Because mesenchymal stem cells are located throughout the body, it is currently impossible to accurately determine the total number that exist during life. One approach to providing an estimate is to determine the number of mesenchymal stem cells in a standard portion of bone marrow. A number of laboratories have attempted to provide such estimates throughout life. At the Skeletal Research Center, at Case Western Reserve University, scientists isolate and purify mesenchymal stem cells and encourage them to attach to and grow on petri dishes, in which the cells form colonies, each of which is derived from one cell. They have developed the technology for isolating, purifying, and expanding mesenchymal stem cells in culture dishes without the mesenchymal stem cells entering any of the differentiation pathways. Based on this technology, Skeletal Research Center scientists have processed fresh bone marrow specimens from hundreds of individuals ranging in age from newborns to people in their eighties and nineties. The rate of cell division and the sensitivity to agents that cause differentiation into the mesengenic lineage pathways appear to be identical among all of these cell preparations, independent of the age of the individual providing the bone marrow specimen. Thus, young and old mesenchymal stem cells appear to be identical in cell culture.

Again, emphasizing that colony counts per sample of bone marrow are crude estimates of the frequency of mesenchymal stem cells in marrow, it is clear that large age differences in the numbers of mesenchymal stem cells exist, from very high levels in newborns (about one in ten thousand nucleated marrow cells) to levels tenfold to one hundred-fold less in older individuals. Thus, when a frail eighty-year-old woman breaks a bone, the slowest step in the repair process is the accumulation of enough mesenchymal stem cells at the break site to form a proper callus. When bone is fabricated around the callus to bridge the broken ends, this bone forms, per osteoblast, about as rapidly as in younger individuals. Thus, both mesenchymal stem cell and osteoblast functioning in older individuals appear to be quite similar; what is quite different is the distribution of, and probably the total number of mesenchymal stem cells available to the repair site. This is in contrast to the number of hematopoietic progenitor or stem cells, which stays relatively constant throughout life at about one per ten thousand nucleated cells. Thus, the process of aging appears to involve a decrease in the number of responsive mesenchymal stem cells, not a decrease in function.

In the context of evolution, those individuals who can maintain the highest concentrations of mesenchymal stem cells throughout life will enjoy a selective advantage with age. This advantage involves the rate of tissue repair (as in the case discussed above for bone), and also is related, in part, to the balance between tissue formation and tissue turnover events. The thesis advanced here is that the embryo has the highest tissue levels of mesenchymal stem cells, and that these levels decline with age. The individuals who can maintain high mesenchymal stem cell levels will be able to maintain high tissue fabrication levels and more effectively balance the natural destructive activities observed in almost every mesenchymal tissue. Since both muscle tissues and the dermis of skin are derived from the same small sectors of somites in embryos, it is interesting to note that the loss of muscle mass with age is correlated with texture changes in the skin. One wonders whether this is because both dermal and muscle cells are on the same biological clock, or because the local titers of mesenchymal stem cells, or their reactivity, is decreasing with age.