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Factors Affecting Connective Tissue Progenitors and Orthopaedic Implications

In adults, stem cell populations and progenitors are present in virtually every organ system. Throughout life, tissues are maintained by these underlying systems of cells that repair and regenerate tissues through the generation of new cells. Modulated by hormonal and local factors, these cells move through a series of hierarchical stages and processes, originating with a rare population of upstream stem cells, and progressing into more numerous, although still rare, populations of downstream transit cells and progenitor cells (Fig. 1) (1). The stages of a stem cell life cycle include: activation, self renewal, proliferation, migration, differentiation, and death or survival (Fig. 2). It is reasonable to hypothesize that factors such as gender, aging, smoking, alcohol, disease states, drugs and toxins are associated with changes in the number of stem cells and the functional parameters that determine their downstream kinetics. In vitro colony forming unit assays provide a valuable window into the number and function of stem cells and progenitor cells in various tissues. Colony forming assays identify cells that will adhere to a surface, such as tissue culture plastic, and go on to proliferate by clonal expansion to form an identifiable cluster of cells. In the case of bone marrow, this type of assay has been refined to provide insight into the concentration and prevalence of connective tissue progenitors (CTPs), including osteogenic and chondrogenic populations. With these tools it is possible to begin to methodically explore and quantify the factors that influence the number and prevalence of CTPsand the relationship between the CTP population and the health of bone and cartilage, as well as their remodeling and repair (2). This article reviews current literature regarding factors affecting CTP populations and their downstream populations.