Enhancement of Cell Viability in Cryopreserved Rat Vascular Grafts by Administration of Regenerating Gene (Reg) Inducers

The regenerative capacity of viable cells remaining in cryopreserved vascular allografts is still unclear. Recently, the regenerating gene (Reg) has been documented to play an important role in various regenerating tissues. Here we show the possibility of Reg induction for the enhancement of cryopreserved vascular allograft viability. Cryopreserved rat aortae were isografted or allografted heterotopically. Fresh isografts were also tested. The transplants were retrieved 3, 6, 9, and 12 days after implantation and the intragraft Reg mRNA was measured by a real-time quantitative reverse transcriptional polymerase chain reaction method. Reg expression was not detected before implantation. Reg expression in cryopreserved isografts gradually increased after transplantation, whereas in fresh isografts or cryopreserved allografts it decreased over time after initial expression. Daily administration of 0.5 g/kg nicotinamide (an agent known to be a potent inducer of Reg) induced intragraft Reg mRNA in cryopreserved allografts (p < 0.05) accompanied by augmentation of the intragraft cell population. Daily administration of 0.5 mg/kg FK506 (an immunosuppressant) induced intragraft Reg mRNA both in cryopreserved isografts and allografts (p < 0.01). We conclude that Reg-inductive therapy shows promise as a novel strategy for enhancing the viability of vascular allografts. Moreover, FK506 may be involved in tissue regeneration as well as immunosuppression.