The characteristic CNS responses to injury including increased cell production and attempts at regenerative repair – implicitly predicted where not directly demonstrated by Cajal, but only now more fully confirmed – have important implications for regenerative therapies. Spontaneous CNS cell replacement compares poorly with the regenerative functional repair seen elsewhere, but harnessing, stimulating or supplementing this process represents a new and attractive therapeutic concept.
Stem cells, traditionally defined as clone-forming, self-renewing, pluripotent progenitor cells, have already proved themselves to be an invaluable source of transplantation material in several clinical settings, most notably haematological malignancy, and attention is now turning to a wider variety of diseases in which there may be potential for therapeutic intervention with stem cell transplantation. Neurological diseases, with their reputation for relentless progression and incurability are particularly tantalising targets. The optimal source of stem cells remains to be determined but bone marrow stem cells may themselves be included amongst the contenders.
Any development of therapies using stem cells must depend on an underlying knowledge of their basic biology. The haemopoietic system has long been known to maintain circulating populations of cells with short life spans, and this system has greatly informed our knowledge of stem cell biology. In particular, it has helped yield the traditional stem cell model – a hierarchical paradigm of progressive lineage restriction. As cells differentiate, their fate choices become progressively more limited, and their capacity for proliferation reduced, until fully differentiated, mitotically quiescent cells are generated. Even this, however, is now under challenge.