Question

The use of cord (umbilical) stem cells for adult haemopoietic transplants is associated with a significant issue related to low stem cell yield. Discuss the methods that have been implemented, and those that are currently under investigation, to improve outcome following cord stem cell transplantation in relation to improvements in the CD34+ cell dose provided.

Answer 1

Umbilical cord blood, like bone marrow and peripheral blood, is a rich source of stem cells for transplantation. There may be advantages for certain patients to have cord blood stem cell transplants instead of transplants with marrow or peripheral blood stem cells (PBSCs). Cord blood for transplantation is collected from the umbilical cord and placenta after a baby is delivered. However, compared with marrow or mobilized peripheral blood stem cell grafts from adult donors, significant delays in the rates and kinetics of neutrophil and platelet engraftment are noted after UCB transplant. These differences relate in part to the reduced numbers of HSCs in UCB grafts. To improve the rates and kinetics of engraftment of UCB HSC, several strategies have been proposed, including ex vivo expansion of UCB HSCs, the addition of third-party mesenchymal cells, intrabone delivery of HSCs, modulation of CD26 expression, and infusion of two UCB grafts.

several unique properties of UCB have been identified. Compared with bone marrow (BM) cells, CD34+/CD38− UCB cells proliferate more rapidly and generate larger numbers of progeny cells [1,2]. In addition, longer telomere lengths of UCB cells have been proposed as a possible explanation for the greater proliferative capacity of UCB. Despite this, the outcomes in adults undergoing HSC transplants with a UCB graft are significantly influenced by the low cell dose of the graft. Numerous clinical studies have consistently demonstrated that the total nucleated cell (TNC) and CD34+ cell doses in cord blood grafts are highly correlated with the rate of neutrophil and platelet engraftment, as well as the incidence of graft failure and early transplant-related complication [5–13]. Based on these studies, critical cell-dose thresholds have been established.

Umbilical cord blood HSC research has revolutionized the unrelated allogeneic field of medicine, now comprising 30% of all unrelated marrow and stem cell transplant procedures performed in the USA annually (Center for International Blood and Marrow Transplant Research ‘Sources of Cells for Transplant’). Little is known about the cellular mechanisms underlying successful donor HSC and T-cell homing and engraftment in vivo despite an infusion of UCB graft CD34 HSC doses ranging generally 1 log less than that of BM or mobilized peripheral cells from adult donors. Use of double cord blood units has been shown to improve the rates and kinetics of UCB engraftment in adult patients.