Preconditioning and cell-based therapeutics

One of the major barriers to cell therapy is the limited and often poor engraftment of stem and progenitor cells in tissues. The “potency” of transplanted cells can be increased by genetic modification or more easily by “preconditioning.” Preconditioning involves applying a sublethal stimulus to protect against a later lethal insult. One of the best-known and most feasible forms of preconditioning is “hypoxic preconditioning.” Stem cells normally reside in a “hypoxic” niche in the body. A large body of evidence demonstrates that hypoxic preconditioning of a wide variety of stem and progenitor cells prior to transplantation increases their survival and engraftment, increases their secretion of trophic and paracrine factors, stimulates tissue repair and remodeling, and facilitates functional recovery. Besides hypoxia, cytokines such as IL-6, drugs such as minocycline, and trophic factors such as stromal derived factor (SDF)-1 and erythropoietin also serve as “preconditioning” agents. Another approach is to “condition” the host tissue. A safe and feasible intervention, remote ischemic conditioning using a blood pressure cuff on the limbs, makes the host more receptive and responsive to transplanted cells, and should be further investigated in preclinical models.