Growth factors - Pharmaceutical Biotechnology: Concepts and Aapplications - page 270

B & T lymphocytes

Stem cell

CFU - S

CFU - GEMM

Basophils CFU-BAS

CFU-GM

BFU-E

CFU-EO

CFU - MEG

CFU-G CFU-M CFU-E

Platelets Eosinophils

Granulocyte

Monocyte Erythrocytes

Figure 10.1 A simplifi ed overview of the haematopoietic process as currently understood. Refer to text for
details (BFU: burst forming unit)

Most of these haemopoietic growth factors are glycoproteins, displaying a molecular mass in the
region of 14-24 kDa. Most are produced by more than one cell type, and several such regulators can
stimulate proliferation of any one haemopoietic cell lineage. This is due to the presence of receptors for
several such factors on their surface. Receptor numbers for any one growth factor are low (less than 500
per cell), and proliferation can be stimulated even when only a small proportion of these are occupied.
During normal haemopoiesis, only a small fraction of stem cells undergo differentiation at any
given time. The remainder continue to self-renew. The molecular detail underpinning self-renewal
is poorly understood. However, it has been shown that certain transformed stem cells can be induced
to undergo continuous proliferation in vitro under the infl uence of IL-3. The concentration of IL-3
is critical, with differentiation occurring below certain threshold concentrations of this cytokine.
The delicate balance between stem cell renewal and differentiation is likely affected not only by
the range of growth factors experienced, but also by the concentration of each growth factor.

10.2.1 The interleukins as haemopoietic growth factors

The interleukin family of cytokines has been overviewed in Chapter 9, and a number of cytokines
are known to infl uence haemopoiesis. The IL-3 receptor, for example, is found on a wide variety
of progenitor haemopoietic cells, and appears to stimulate not only CFU-GEMM, but also the
precursor cells of basophils, eosinophils and platelets. The role of IL-11, which also plays a role,
was also discussed in Chapter 9.