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Marrow Stem Cells, Mesenchymal Progenitor Cells, and Stromal Progeny

During development, embryonic stem cells (ES) have been thought traditionally to give rise to organ-restricted stem cells. This process is believed to occur as a continuum through adult life since these stem cells also give rise to lineage committed progenitor cells, which retain a certain degree of multipotentiality in adult tissues. An example is the CFU-GEMM of the hematopoietic system which renews the formed elements of the blood. Tissue restricted stem cells and progenitor cells have been described for all adult tissues including bone marrow, liver, and brain. Quiescent stem cells that are retained in adult hematopoietic and non-hematopoietic tissues may be recruited from the quiescent state (G0) and mobilized when tissues are injured or depleted. They eventually form committed progenitor cells which differentiate to mature (terminal) cells that express genes that are functionally tissue specific. Differences exist between the hematopoietic and nonhematopoietic regenerative processes. Injury to or depletion of hematopoietic cells provokes replacement of blood or immune elements by newly generated cells derived from committed progenitor cells in the marrow microenvironment. In contrast, repair mechanisms associated with non-hematopoietic tissues may involve cells which appear mature, but which have retained some degree of proliferation and differentiation potential. Examples are hepatocytes, skin fibroblasts, endothelial cells, and smooth muscle cells. Previously, the differentiation potential of mesenchymal progenitor cells (MPC) or stromal progenitor cells in the bone marrow has been thought to be limited to the generation of hematopoietic supportive stromal cells of