Transplantation of cord blood stem cells for treating hematologic diseases and strategies to improve engraftment

Umbilical cord blood (CB) offers an alternative source of hematopoietic stem cells (HSCs) to treat patients with malignant and non malignant hematologic diseases, such as leukemia, lymphoma, myeloma, Fanconi anemia, myelodysplasia and sickle cell anemia [1]. Umbilical CB contains a low cell dose, and the first transplantation CB was performed in children with Fanconi anemia, by Gluckman and collaborators at the hospital Saint Louis in Paris in 1989 [2]. Since then, CB transplantations have been performed with success in children, but also in adults. However, low cell dose, graft failure, poor engraftment in the bone marrow (BM), and delay in engraftment and immune reconstitution lead to significant morbidity and mortality, particularly in adults. The rate of morbidity and mortality after CB transplants remains high in adults, with 47% of patients dying within 100 days of the unrelated transplant [3]. To improve the rate of success of CB transplantation, double doses of CB units are being infused into patients. However, this limits the availability of CB for therapy, conditions are still suboptimal and it does not address the main limitations of CB for the treatment of hematologic diseases. CB is considered a standard source of HSCs for pediatric transplants, and the transplantation of HSCs from CB is a viable alternative even in adults, as demonstrated by the number of adult patient transplants exceeding the number in child patients in the last 2–3 years [4–7]. Umbilical CB contains threeto six-times more repopulating hematopoietic progenitor and stem cells than the BM and mobilized peripheral blood (MPB) [8]. It is depleted of immune cells, particularly T lymphocytes, and has decreased natural killer cell activity, reduced alloproliferative, allostimulatory and allocytolytic capacity of mononuclear cells, and a lower frequency of alloreactive cytotoxic T lymphocyte precursors in CB mononuclear cells [9,10]. This allows for greater disparity of HLA antigens when matching donors to recipients than with BM and MPB. Currently, worldwide donor registries include over 14 million donors, including 8 million Americans, and the CB inventory represents only a small fraction of them. The registry of potential BM donors meets the needs of an estimated 60% of Caucasians in the USA, and only 5–15% of minorities. The chance that siblings will be a match is only 25%. Hence, umbilical CB provides an alternative model for unrelated allogeneic transplantation of HSCs and for potentially treating more patients, particularly minorities who are underrepresented in BM registries. Novel strategies are being devised and considered to address the main limitations of umbilical CB for transplantation, and are Umbilical cord blood (CB) offers an alternative source of hematopoietic stem cells for the treatment of malignant and nonmalignant hematologic diseases. Umbilical CB has high levels of repopulating hematopoietic stem cells and is depleted of immune cells. It elicits low cell dose, and delayed and poor engraftment to the bone marrow. Umbilical CB is used for pediatric transplants as well as in adults. CB transplantation is associated with a high rate of mortality and morbidity, particularly in adults. To improve the success rate, patients are treated with a double CB dose. However, such a strategy limits the availability of CB transplants for patients and the conditions are still suboptimal. Novel avenues are being devised and considered; among them the expansion and propagation of CB stem cells in vitro, and the improvement of homing and engraftment of CB stem cells to the bone marrow. Such strategies would overcome the low cell dose in CB units by improving the delay and engraftment of CB stem cells to the bone marrow. Therefore, it would reduce the risk of early infections, improve the success rate of CB transplantation and make CB transplantation available to more patients. Umbilical CB offers a promising model for cellular therapy and regenerative medicine.