Stem cell populations decline in activity with age, and the hematopoietic stem cells resident in bone marrow, responsible for generating blood and immune cells, are no exception. Their decline is one of the contributing factors leading to immunosenescence and inflammaging, the aging of the immune system. With age, the immune system becomes less effective in its tasks of destroying pathogens and errant cells, but also becomes chronically overactive at the same time. The result is inflammation, disruption of tissue regeneration, growing risk of cancer, increasing numbers of senescent cells, and vulnerability to infection.
Restoration of the hematopoietic stem cell population is one of the three necessary arms of immune rejuvenation. This will require advances in control over cell behavior, but is not too far beyond the present state of the art. The first generation of cell therapies resulted in cell transplants that near all die rather than engraft and participate in tissue maintenance. Today’s stem cell therapies for the most part produce benefits due to temporary shifts in cell signaling brought about by the transplanted cells prior to their death. Reliable approaches by which large fractions of transplanted hematopoietic stem