Pleiotrophin and its Role in Regulating Haemopoietic Stem Cell Regeneration

HSCs are cells that have the capacity to self renew, proliferate and differentiate, providing cells of the mature blood system throughout a lifetime. The concept of such a cell was first considered in 1961 subsequent to the injection of healthy marrow into a lethally irradiated recipient mouse which mediated the reconstitution of mature blood cells in the irradiated host(Till and Mc Culloch, 1961). This finding provided preliminary experimental evidence that all of the blood cells were derived from a single type of progenitor cell, also known as HSC. The majority of mature blood cells have a limited life span, red blood cells survive for 120 days and some white cells just hours, thus requiring their continuous replacement to sustain life. Replenishment of the mature blood cells does not occur as a direct single step but is in fact achieved through the production of progenitor cells that display diminished self-renewal capabilities with increased maturity and the assembly of HSC hierarchy. HSCs differentiate to multi-potent progenitors (Allen.D, 1984). These multi-potent progenitors have the ability to differentiate into either myeloid or lymphoid progenitor cells. Lymphoid progenitor cellsgive rise to T, B and Natural Killer (NK) cells while the myeloid progenitor cell gives rise to neutrophils, basophils, eosinophils, red cells, platelets and monocytes/macrophages (figure 1) all of which require constant replenishment to keep circulating blood levels constant. This method of mature blood cell production allows a large number of mature cells to be derivedfrom a small population of HSCs. (Lajtha, 1979