Blood, 1 November 2001, Vol. 98, No. 9, pp. 2595-2595
Multipotent human cells expand indefinitely
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.
Diane S. Krause
Yale University School of
Medicine
