BACKGROUND: The establishment of donor-derived hematopoiesis in the recipients of hematopoietic stem cell (HSC) transplants involves extensive proliferation and differentiation of HSCs. Data from long-term survivors of HSC transplants suggest that these transplanted HSCs may experience a debilitating replicative senescence. A significant posttransplant shortening of peripheral blood mononuclear cell (PBMNC) telomeres has been observed in both marrow transplant and peripheral blood progenitor cell transplant recipients. Similar studies have not been performed for umbilical cord blood (UCB) HSC transplants, which might be expected to exhibit increased posttransplant replicative potential due to their inherently greater telomere length. STUDY DESIGN AND METHODS: Blood was obtained from donor-recipient pairs of allogeneic PBHSC transplant and UCB HSC transplant, both before transplant and at follow-up treatments (minimum 1 year after transplant) after engraftment. Telomere restriction fragment length (TRFL) analysis was performed on the blood samples. The mean TRFL and posttransplant changes in the mean TRFL were analyzed. RESULTS: Measurements of telomere lengths in the PBMNCs of transplant patients revealed a significant net decrease in telomere length in all transplant recipients compared with their respective donors. Our results also revealed that the PBMNCs of umbilical cord stem cell transplant patients retain a significantly longer posttransplant telomere length. CONCLUSION: The significantly longer telomeres observed in the allogeneic UCB HSC transplant recipients compared to the allogeneic PBHSC transplant recipients in our study may be indicative of a replicative advantage inherent in the use of UCB HSC for transplant.
BACKGROUND: The establishment of donor-derived hematopoiesis in the recipients of hematopoietic stem cell (HSC) transplants involves extensive proliferation and differentiation of HSCs. Data from long-term survivors of HSC transplants suggest that these transplanted HSCs may experience a debilitating replicative senescence. A significant posttransplant shortening of peripheral blood mononuclear cell (PBMNC) telomeres has been observed in both marrow transplant and peripheral blood progenitor cell transplant recipients. Similar studies have not been performed for umbilical cord blood (UCB) HSC transplants, which might be expected to exhibit increased posttransplant replicative potential due to their inherently greater telomere length. STUDY DESIGN AND METHODS: Blood was obtained from donor-recipient pairs of allogeneic PBHSC transplant and UCB HSC transplant, both before transplant and at follow-up treatments (minimum 1 year after transplant) after engraftment. Telomere restriction fragment length (TRFL) analysis was performed on the blood samples. The mean TRFL and posttransplant changes in the mean TRFL were analyzed. RESULTS: Measurements of telomere lengths in the PBMNCs of transplant patients revealed a significant net decrease in telomere length in all transplant recipients compared with their respective donors. Our results also revealed that the PBMNCs of umbilical cord stem cell transplant patients retain a significantly longer posttransplant telomere length. CONCLUSION: The significantly longer telomeres observed in the allogeneic UCB HSC transplant recipients compared to the allogeneic PBHSC transplant recipients in our study may be indicative of a replicative advantage inherent in the use of UCB HSC for transplant.