Multipotential cord blood cells. Are they the future?

Authors


This issue of the British Journal of Haematology is devoted to the emerging field of cord blood transplantation (CBT), with articles from some of the world leaders in this area. As described succinctly by Eliane Gluckman in her article, the first cord blood transplant was reported in 1989. It was successful and since then cord blood applications for both haematopoietic transplantation and for cellular therapy has rapidly expanded. We felt it was timely to bring together a review of these advances to explore the field more fully.

There are advantages and disadvantages in the use of cord blood for transplantation. They are ‘off the shelf’, ready to go, pre-tested (including stem cell content, human leucocyte antigen [HLA] type and infectious agents) with a median time to transplant 25–36 d earlier than other donor types. The tolerance of mismatch is greater with lower graft-versus-host disease (GVHD) and no risk to the donor, making this attractive. However, early data from CBT reported mixed results, indicating a necessity to further investigate crucial aspects of cord blood cell biology and transplantation. The purpose of this issue is to bring together experts within this field and to provide an overview of current practices in CBT, from the establishment of cord blood banks, to changes in transplant regimes aimed to increase the outcome of transplants, and finally, to point out the exciting opportunity that banking of cord blood may provide as a stem cell source for cellular therapy in the field of regenerative medicine.

Smith et al provide an important review of the use of cord blood as an alternative to other haematopoietic stem cells. They discuss the decision regarding what stem cell source to use in the absence of a related donor, which may depend on the urgency of transplant, the size of the patient and the potential need for donor lymphocyte infusion, but conclude that, in patients where a certain degree of mismatch was considered acceptable to enhance the graft-versus-leukaemia (GVL) effect, a 6/6 HLA-matched umbilical cord blood transplant with an adequate cell dose should be considered first line. Although a bone marrow-derived source may be more practical in adults due to the limited cell dose in cords, this is less of a problem in children who continue to show improved survival rates, as discussed by Locatelli et al. Following the realisation of the importance of stem cell dose for engraftment and survival, further reviews analyse parameters that may be employed to improve its utility. Rocha discusses the importance of HLA matching and stem cell dose, including an algorithm for choosing a cord blood unit while Delaney at al present different transplant regimes and how the use of more than one cord blood unit can provide an adequate nucleated cell dose to successfully engraft an adult recipient, improving not only engraftment but also overall survival with a potential for decreasing the relapse rate in high risk disease. Finally in this group of clinical outcome papers, Fernandez et al discuss how the addition of third party cells, including haploidentical-derived CD34 cells can help transition during the prolonged period of neutropenia following CBT, allowing earlier engraftment and better overall survival.

In addition to the potent haematopoietic stem cells present in a cord blood unit, the prevalence of other immature cells in cord blood is exciting and has led to the idea that cord blood can be used for cellular therapy. Harris discusses the ability of CB stem cells to regenerate numerous tissue types. Clinical trials are underway in type 1 diabetes, cerebral palsy and peripheral vascular disease. These cells may work by reducing inflammation in stroke models, protecting nervous tissue from apoptosis and preventing nerve fibre reorganisation. Particularly promising are the early results in type 1 diabetes, thought to be related to cord blood-derived stem cells differentiating into new islet cells and mediating immune tolerance to these cells. However, the contribution of naive regulatory T cells cannot be ignored. Regulatory T cells from cord units might have a more suppressive activity than those derived from adult sources. Harnessing these cells, as well as mesenchymal stem cells, found both in cord blood units and in the umbilical cord itself may contribute to the low levels of GVHD seen following CBT and have the potential for alternative therapeutic uses as discussed by Tolar et al. Finally, Verneris et al discuss the potential for cord blood natural killer cells to enhance the GVL effect. If this can be established, and as better ability to provide viral-specific T cells from cord blood is achieved, the outcome of CBT will improve further.

These encouraging results suggest a concerted action within countries to develop comprehensive cord blood banking programmes. Given improving clinical results and the lack of risk to the donor, how should health leaders approach the concept of providing a cord blood bank which encompasses the need of the nation? Public banks in the US and Europe were first established in 1993 and 1994, respectively. Over 450 000 units have been banked worldwide in more than 50 banks. Navarrete et al give an overview of these first developments in cord blood banking and Querol et al bring us up to date in current concepts of banking with an attempt to answer the critical question of how many cord blood units should be banked in order to serve the nation.

We hope that you will enjoy ‘the journey’ through this exciting themed issue of the British Journal of Haematology!

Ancillary