Differentiation of mesenchymal stem cells

Fig. 3. Model of stem cell differentiation.
A.Deterministic model.
B.Stochastic model.
C.Differentiation model of mesenchymal stem cells.


Retroviral labeling of individual cells is a useful clonal assay to monitor lineage commitment at the single cell level. At present, several models have been proposed in which hematopoietic lineage determination is driven intrinsically 68), extrinsically 69), or both 70). The issue of the mechanism and the extent of cellular differentiation that occurs when stem cells begin to differentiate is the area of furthest advanced research. Two models have been proposed: a deterministic model, in which differentiation is governed by the microenvironment (including growth factors and cytokines), and a stochastic model, in which differentiation, self-replication and the direction of differentiation emerge somewhat randomly (Fig. 3A, B). The different models arise from different conceptions of mesenchymal stem cells. The mesenchymal stem cell (MSC2) line is stochastically committed toward the cardiac lineage, and following this commitment, they proliferate as transient amplifying cells and differentiate into cardiac myocytes (Fig. 3C).

Considering stem cell transplant as a therapy, when mature cells arising from hematopoietic stem cells are needed, as in marrow transplant, there are no problems attending cellular differentiation. However, in the case of cells that serve to originate cells of several different organs, as in the case of mesenchymal stem cells, there is a possibility for differentiation to cells not needed in the treatment. Ectopic tissue may therefore emerge from implanted mesenchymal stem cells, especially where the buffering system from a given site is lost and the stem cells begin to differentiate randomly into cells differing from the implanted site, thereby creating unwanted ectopic tissue.