Evidence for the hypothesis that there are stromal stem cells present in the soft connective tissues associated with marrow and bone surfaces that are able to give rise to a number of different cell lines is reviewed. The lines are currently designated fibroblastic, reticular, adipocytic and osteogenic. Fibroblastic colonies, each derived from a single colony-forming unit fibroblastic (CFU-F), are formed when marrow cells are cultured in vitro. In vivo assays of tissue formed by CFU-F in open transplant or in diffusion chambers, have demonstrated that some CFU-F have a high ability for self renewal and multipotentiality whereas some have more limited potential. Preliminary investigations in vitro also support the hypothesis and have shown that CFU-F are a heterogeneous population of stem and progenitor cells and that their differentiation in vitro can be modified at the colony level. The stromal cells which survive and proliferate in vitro are highly dependent on culture conditions. The number and hierarchy of cell lines belonging to the stromal fibroblastic system are not yet fully elucidated and more specific markers and better assays for the different phenotypes are required before a greater understanding can be achieved. The possibility that the marrow stromal system is part of a wider stromal cell system of the body is proposed.

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