THE CONTEXT
Regeneration combines proliferation of surviving cells with the production of mature cells from stem cells.
Signals driving cell proliferation
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Growth factors and the extracellular matrix (ECM) provide signals that drive cell proliferation. Some growth factors act on multiple cell types, whereas others are cell selective.
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Growth factors are usually produced near the injury. Activated macrophages are their most important source, although epithelial and stromal cells also produce them.
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Several growth factors bind ECM proteins, which display them at high concentrations at the injury site.
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All growth factors activate signaling pathways that stimulate cell division. Cells also bind ECM proteins through integrins, whose signals can stimulate proliferation.
Embryonal and tissue stem cells
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Embryonal stem cells are described as self-renewing, totipotential cells capable of giving rise to all mature cell lineages.
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Tissue stem cells occur in most adult tissues. Compared with embryonal stem cells, they have more limited self-renewal capacity and typically generate cells of their resident tissue.
Asymmetric division and injury responses
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Asymmetric cell division produces one daughter cell that remains a stem cell and another that begins to differentiate. This supports both self-renewal and production of mature cells.
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Tissue stem cells occupy specialized niches. Injury generates signals that stimulate their proliferation and differentiation to repopulate the damaged tissue.
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Their contribution is especially relevant when surviving differentiated cells have limited or no intrinsic proliferative capacity.