Physiological Changes: Stem Cells

Skeletal maturity is observed in the early to mid-thirties in modern, well-nourished humans. However, the process of growth that has occurred into the thirties from embryology occurs on a backdrop of continued tissue replacement Figure 1 Mesengenesis. SOURCE: Author or rejuvenation, referred to as tissue turnover. In bone, for example, there is a constant destruction of bone tissue followed by refabrication of the lost bone to the extent that the entire skeleton is replaced every two to ten years, depending on the age of the individual. This is in addition to the continued growth or expansion of bone that occurs from birth through the teenage years. Thus, in early life, the process of bone formation far exceeds the process of bone loss. Importantly, osteoblasts, the bone-forming cells, form sheets of many cells that fabricate layers of new bone. The extent of such bone formation is directly related to how many osteoblasts are in this formative sheet. These osteoblasts also have a genetically fixed life span—a week to two weeks for most humans. Thus, while sheets of osteoblasts are fabricating bone in various locations within the body, some osteoblasts are dropping dead. Their place in the fabrication sheets is taken by newly born osteoblasts—it takes two or three generations of osteoblasts to fill the holes in the bone formed by the natural bone-destruction process. Therefore, mesenchymal stem cells must be present in sufficient numbers to provide descendants that traverse the differentiation pathway to become newly born osteoblasts. In adults, these mesenchymal stem cells are in the bone marrow in close proximity to bone and are associated with blood vessels that nourish bone.

Another way of stating that skeletal maturity peaks in a person's thirties is to say that the process of bone destruction becomes equal to the process of bone fabrication. As a person progresses in age past the thirties, the destructive process exceeds the formative events, resulting in cumulative bone loss, which is referred to as osteoporosis when the bone structure becomes fragile and susceptible to fracture. Although osteoporosis is considered a disease of the aged, the extent of bone loss and severity is dependent on the bone stock present in a person's thirties and the relative balance of bone formation versus destruction thereafter. Clearly, a key variable in this complex process is the number of mesenchymal stem cells in a particular location—and the number of their progeny that are cued into the bone-forming pathway at any one time.