Scientific publications
1. Long term cryopreservation of umbilical cord blood stem cells
The long-term cryopreservation of umbilical cord blood stem cells is critical in consideration of umbilical cord blood banking activities in anticipation of its human application, independent from its autologous or allogeneic use. It is important in this perspective not only that a sufficient number of viable cells can be recovered after cryopreservation, but also that their proliferative capacity, their functionality and their engraftment potential is preserved as well, illustrating their effectiveness for clinical application upon cryopreservation. There is today ample literature with representative real-time data to document that applying (automated) programmed control freezing conditions in combination with established cryopreservation media and well described procedures for thawing, these criteria can be matched, supporting long term storage for periods up to 15 years at ultra-low temperatures (ref. 1-4). These data furthermore indicate that qualified conditions can guarantee much longer periods of cryopreservation; an expiration date, if any, still has to be established.
2. Autologous vs. allogeneic stem cell therapy
According to a recent report of the European Group for Blood and Marrow Transplantation (EBMT; ref. 5) there were in total 24.168 first haematopoietic stem cell transplantations (HSCT) in 2005, 15.278 autologous (63%), 8.890 allogeneic (37%), and 3.773 additional re- or multiple transplants, reported from 597 centres in 43 participating countries. Main indications were lymphomas (13.825 (57%; 89% autologous)), leukaemias (7.404 (31%; 82% allogeneic)); solid tumours (1.655 (7%; 92% autologous)) and non-malignant disorders (1.131 (5%; 93% allogeneic)). Compared to 2004, there was a 20% increase in allogeneic HSCT; numbers of autologous HSCT remained constant. The most noticeable increase was in unrelated HSCT, which comprise 41% of all allogeneic HSCT. Unrelated HSCT were preferentially performed for leukaemias, the prenatal origin of childhood leukaemias preventing autologous HSCT. Hence, autologous HSCT is considered as challenging and controversial in childhood leukaemia, although the incidence of pre-leukemic clone is ~100 times that of the incidence of childhood leukaemia (ref. 6), indicating that a second - post-natal - trigger would be necessary for the clinical development of childhood leukaemia. The first autologous cord blood transplantation for treatment of a child with leukaemia was only reported early 2007 (ref. 7).
The mean cost for an allogeneic HSCT in The Netherlands is 70.446 €, substantially higher as compared to 40.593 € for an autologous HSCT; the mean additional cost to identify a suitable donor for allogeneic HSCT is equal to 42.000 € (ref. 8), and the disease tends to progress to advanced or high risk stage while searching for a suitable donor. These numbers indicate a clear pharmaco-economic effect in favour of autologous HSCT, whenever possible. The earlier timing might contribute to better clinical outcome because disease progression can be prevented and accumulation of e.g. chemotherapy-induced tissue toxicity can be decreased. Furthermore, chronic immunosuppression is very often required with allogeneic HSCT, reducing the quality of life even further.
3. Umbilical cord blood transplantation versus bone marrow or mobilised peripheral blood stem cell transplants
Risks and benefits of umbilical cord blood have become clear compared to bone marrow or mobilized peripheral blood derived stem cells (ref. 9). The collection of umbilical cord blood after birth carries no risk for the donor. Collected umbilical cord blood can be cryopreserved and stored for prolonged periods. Umbilical cord blood units are immediately available upon request and can be shipped to any transplant centre in the world with relative ease. Umbilical cord blood transplantation is associated with a lower incidence of acute Graft Versus Host Disease (GVHD), and partial HLA match between the donor and recipient is tolerable. There is also a reduced - negligible - risk of infectious disease transmission from umbilical cord blood. From a clinical perspective, no other area of stem-cell biology has so far been applied so successfully as has transplantation of umbilical cord blood stem-cells for the treatment of blood diseases, focusing on its use to reconstitute bone marrow.
Favourable results from a prospective study comparing cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell based transplants from related donors in adult patients with haematological malignancies were published (ref. 10), suggesting that unrelated cord blood could be a stem-cell source as safe and effective as related bone marrow or mobilized peripheral blood when used as a primary source, when applied at the same time as for patients who had a related donor, i.e. before the disease progresses to advanced or high risk stage while searching for compatible donor. However, rather than focusing on the use of umbilical cord blood stem cells for bone marrow reconstitution, particularly in the context of their greater differentiation plasticity and multipotency as compared to e.g. post-natal adult stem cells, they should be regarded as a highly valuable source for future tissue generation (vide infra).
4. Autologous umbilical cord blood stem cells
For acquired and genetic disorders of haematopoiesis, umbilical cord blood transplantation has been applied extensively in the allogeneic setting. Concerning the use of autologous umbilical cord blood transplantation, there is considerable less experience, as a result of the great controversy about the role of autologous umbilical cord blood collection and storage. Despite this controversy and the recent phenomenon of private umbilical cord blood storage, however, some cases have been reported in the scientific literature for the successful treatment of stage IV neuroblastoma (ref. 11), severe aplastic anemia (ref. 12) as well as for the controversial and challenging treatment of a child with leukaemia (ref. 7), clearly illustrating its significant clinical potential.
Several well documented examples clearly illustrate the significant potential of (autologous) umbilical cord blood stem cells in the emerging field of regenerative medicine. Tissue-engineered living blood vessels generated from umbilical cord progenitors represent a promising new option for the repair of congenital malformations (ref. 13). The induction of stem cells from umbilical cord blood into insulin-producing islet-like structures, which co-express insulin and C-peptide, might have a significant potential to advance human UCB derived stem-cell-based therapeutics for diabetes (ref. 14). Recently, British scientist from Newcastle University announced the world’s first artificial liver created from umbilical cord blood, but still have to author a scientific article (ref. 15).
11 February 2007, Mechelen, Belgium
© Cryo-Save AG
References:
1. Kobylka et al, Transplantation 65 (9), 1275-1278 (1998);
2. Spurr et al, Cryobiol. 44, 210-217 (2002);
3. Broxmeyer et al, Proc Natl Acad Sci. SA 100 (2), 645-650 (2003);
4. Moezzi et al, Transpl Proc. 37, 4500-4503 (2005);
5. Gratwohl et al, Bone Marrow Transplantation 39, 71-87 (2007)
6. Mori et al, Proc Natl Acad Sci. USA 99, 8242-8247 (2002);
7. Hayani et al, Pediatrics 119, 296-300 (2007);
8. Tan et al, iMTA Report nr. 06.80 (2006);
9. Brunstein & Wagner, Annu Rev Med 57, 403-417 (2006);
10. Takahashi et al, Blood 109 (3), 1322-1330 (2007);
11. Ferreira et al, Bone Marrow Transplantation 24, 1041 (1999);
12. Fruchtman et al, Biol Blood Marrow Transpl. 10, 741-742 (2004);
13. Schmidt et al, Ann. Thorac Surg 82, 1465-1471 (2006);
14. Sun et al, Biochem Biophys Res Commun. 354, 919-923 (2007);
15. Daily Mail, October 31st, 2006.
