Skeletal Resident Stem Cells

Bone is a specialized type of connective tissue with a specialized extracellular matrix impregnated with hydroxyapatite crystal, which gives bone the characteristic of a hard tissue, with limited flexibility. The three main cell types that participate in bone formation and maintenance are the osteoblasts, osteocytes, and osteoclasts. Osteocytes are considered the mature end point cell of the osteogenic lineage cascade. Osteoblasts are bone-producing cells, which synthesize and secrete collagen fibers and other noncollagen proteins and begin the process of mineralization of bone matrix. Osteoclasts are the third specialized cell type found in bone tissue and are responsible for bone resorption. Osteoblasts and osteocytes derive from a common precursor, identified as a mesenchymal stem cell, also known as stromal stem cell or skeletal stem cell. Under proper conditions, these cells give rise to colonies of fibroblastoid cells, each colony derived from a single cell clone, a single precursor, termed a colony forming unit–fibroblast (CFU-F). These stem cells are also recognized by their differentiation potential. Because of their ability to be grown in vitro without losing their multipotency, mesenchymal stem cells have been explored in the repair or regeneration of injured mesenchymal tissues such as fracture repair, tendinous lesions, and cartilage. In the bone marrow microenvironment, skeletal stem cells are not randomly distributed. They are located mainly around the precapillary arteriole, a site identified as a perivascular niche. This intimate functional and morphologic relationship led to the observation of a widespread distribution of mesenchymal progenitors in the whole organism. Both endothelial and mesenchymal cells have been shown to be essential in the bone treatment. Although the main focus of using mononuclear cells in the regeneration and reconstruction of bone tissue is the combined action of osteoprogenitor cells and angioblasts, several groups described a likely paracrine activity by lymphocytes and monocytes present in this population. These cells secrete cytokines such as interleukin-6 and TGFb, which stimulate the proliferation and differentiation of cells from the bone and the vascular system. However, these studies are very recent and real paracrine effects still need to be clarified.