Mesenchymal Stem Cells - Interest Group
The presence of nonhematopoietic stem cells in bone marrow was first
suggested by the observations of the German pathologist Cohnheim 130
years ago. His work raised the possibility that bone marrow may be the
source of fibroblasts that deposit collagen fibers as part of the normal
process of wound repair.
Evidence that bone marrow contains cells that can differentiate into other
mesenchymal cells, as well as fibroblasts, is now available, starting with
the work of Friedenstein and colleagues. They placed whole bone marrow
in plastic culture dishes and removed the nonadherent cells after 4 hours,
thus discarding most of the hematopoietic cells. They reported that the
adherent cells were heterogeneous in appearance, but the most tightly
adherent cells were spindle-shaped and formed foci of two to four cells,
which remained inactive for 2–4 days and then began to multiply rapidly.
After passaging several times in culture, the adherent cells became more
homogeneously fibroblastic in appearance.
They also found that the cells could differentiate into colonies that resembled small deposits of
bone or cartilage. Friedenstein's observations were extended by other groups throughout the
1980s, and it was established that the cells isolated by Friedenstein's method were multipotential
and could differentiate into osteoblasts, chondrocytes, adipocytes, and even myoblasts.
Subsequent experimentation also how their fate could be determined by environmental cues.
Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid,
inorganic phosphate, and dexamethasone could promote their differentiation into osteoblasts. In
contrast, the addition of transforming growth factor-beta (TGF-b) could induce chondrogenic
They are currently referred to as either mesenchymal stem cells (MSCs), because of their ability
to differentiate into mesenchymal-type cells, or as marrow stromal cells, because they appear to
arise from the complex array of supporting structures found in the marrow.
Key Historical Articles:
- Becker AJ, McCulloch EA, Till JE (1963). "Cytological demonstration of the clonal nature of
spleen colonies derived from transplanted mouse marrow cells". Nature 197: 452–4. doi:
10.1038/197452a0. PMID 13970094.
- Siminovitch L, McCulloch EA, Till JE (1963). "The distribution of colony-forming cells among
spleen colonies". Journal of Cellular and Comparative Physiology 62: 327–36. doi:10.1002
/jcp.1030620313. PMID 14086156.
- Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow
IA (1974). "Precursors for fibroblasts in different populations of hematopoietic cells as
detected by the in vitro colony assay method". Exp Hematol 2 (2): 83–92. PMID 4455512.
- Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). "Fibroblast precursors in normal and
irradiated mouse hematopoietic organs". Exp Hematol 4 (5): 267–74. PMID 976387.
- Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997;
- Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated
mouse hematopoietic organs. Exp Hematol 1976;4:267–274.
- Ashton BA, Allen TD, Howlett CR et al. Formation of bone and cartilage by marrow stromal
cells in diffusion chambers in vivo. Clin Orthop Relat Res 1980;151:294–307.
- Bab I, Ashton BA, Gazit D et al. Kinetics and differentiation of marrow stromal cells in
diffusion chambers in vivo. J Cell Sci 1986;84:139–151.
- Castro-Malaspina H, Gay RE, Resnick G et al. Characterization of human bone marrow
fibroblast colony-forming cells (CFU-F) and their progeny. Blood 1980;56:289–301.