The discovery of mesenchymal stem cells is credited with Alexander Friedenstein and associates, who over 40 years ago demonstrated that pieces of bone marrow transplanted under the renal capsule of mice formed a heterotopic osseous tissue thai was self-maintaining, self-renewing, and capable of supporting host cell hematopoiesis. Furthermore. Friedenstein showed that the osseous-forming activity of bone marrow was contained within the fibroblastoid cell fraction isolated by preferential attachment to tissue culture plastic. These findings confirmed that bone marrow contained separable stem cell populations capable of generating hematopoietic and connective tissue cell lineages. These studies also demonstrated that marrow-derived, plastic adherent fibroblastic (stromal) cells were capable of supporting the growth and differentiation of various hcmalopoictic cell types. These cells were then used as feeder layers to establish long-term bone marrow cultures in vitro, which fostered a wealth of new knowledge regarding the molecular mechanisms regulating hematopoiesis.