Biomedical Engineering Reference
In-Depth Information
Long-term HSC
Self-renewal
Self-renewal
Short-term HSC
Multipotent progenitor
Common lymphoid
progenitor
Common myeloid
progenitor
Megakaryocyte
erythrocyte
precursor
Granulocyte
macrophage
precursor
T cells
B cells
NK cells
Erythrocytes
Platelets Granulocytes
Macrophages
Fig. 1 Diagrammatic representation of the HSC and the cell lineages produced from it. Only
long-term and short-term stem cells undergo self-renewal. The multipotent progenitors do not
undergo self-renewal, but give rise to common myeloid and common lymphoid progenitors,
which through several proliferation and differentiation steps, give rise to the mature cells of
the hematopoietic system
Candidate human HSCs are characterized as CD34
+
lin
CD38
(Miller
et al. 1999) and these cells have the ability to repopulate SCID mice. However,
for clinical and the majority of research purposes, HSCs tend to be isolated on
the basis of CD34 expression only, resulting in a heterogeneous population of
which only a small proportion are multipotent HSCs. The CD34 antigen is a
transmembrane glycoprotein and member of the sialomucin family (Simmons
et al. 2001). Although its precise function is unknown, CD34 is believed to be
involved in cell adhesion.
1.1 Early Evidence for the Existence of HSCs
In the 1950s, early studies of murine hematopoiesis, using lethally irradiated
recipient mice and marker chromosomes to separate host and donor cells
demonstrated reconstitution of the entire hematopoietic system from bone
marrow cells (Ford et al. 1956). However, it was not until 1961 that Till and
McCulloch provided evidence for the existence of multipotent HSCs (Till and
