Our ability to dissect out the mechanisms of stem cell self-renewal and differentiation is enhanced by in vitro models for differentiation down multiple lineages. This is one of the primary reasons that embryonic stem cells are so important. But as debate rages regarding use of human embryonic stem cells, work on other human stem cell populations with high plasticity continues. Reyes and colleagues (page 2615) show that nonhematopoietic primary bone marrow cells, obtained from human donors ages 2-50 and grown in vitro for over a year, maintain the ability to differentiate in vitro into multiple cell types. Depending on the culture conditions, the cells differentiate into uniform populations of myocytes, osteoblasts, chondrocytes, adipocytes, or endothelial cells, all of which constitute mesenchymal tissues. The authors therefore call these cells mesodermal progenitor cells (MPCs). MPCs can also form a stromal layer that supports long-term hematopoietic cell survival. Previously, it was unknown whether the same marrow-derived cells could both support hematopoiesis and form mesenchymal tissues. Of note, the authors did not identify conditions in which MPCs differentiate into hematopoietic cells, also of mesenchymal origin.

These are novel and important findings because they indicate for the first time that multipotent human primary cells can be cultured and expanded indefinitely while maintaining their plasticity. This difference from mesenchymal stem cells described previously (Pittenger et al, Science. 1999;284:143-147; Phinney et al, J Cell Biochem. 1999;72:570-585) may be due in part to growing the cells on fibronectin-coated plates at low density. Potential clinical uses of MPCs expanded in vitro include autologous transplantation into growing or healing tissues or use as a stromal support layer for hematopoietic cells. MPCs could also potentially be used for allogeneic transplantation, as they have neither HLA-Dr nor HLA1 surface expression and therefore may elude immune rejection. Also, MPCs can be infected with retroviral vectors and could be used in gene therapy approaches. Perhaps most critical for basic science applications, dissection of the molecular mechanisms of stem cell self-renewal and cell differentiation can be performed using these cells.

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