In 1988, the first umbilical cord blood transplant was performed on a 5-year-old patient with Fanconi anemia, a rare autosomal recessive disorder in the bone marrow that causes bone marrow failure and a consequent decrease in blood cell production.3,7 Following the success of this pioneering medical procedure, it was revealed that umbilical cord blood, which was once often discarded as medical waste, could serve as a potentially valuable therapeutic tool. Now, it has been integrated into treatment plans for several blood disorders, such as leukemia, Hodgkin’s lymphoma, and genetic blood disorders other than Fanconi anemia.2 Cord blood refers to blood extracted from the umbilical cord after childbirth and is particularly advantageous as it contains hematopoietic stem cells, very small embryonic-like stem cells (VSELs), and mesenchymal cells.1 The blood transplant serves as a replacement for abnormal blood cells that cause a blood disorder for the patient.3
Before umbilical cord blood transplants, bone marrow transplants were the traditional method for treating blood disorders. However, it is more difficult to find a proper donor match due to the need for human leukocyte antigens (HLAs) to match as much as possible. HLAs are genes that code for major histocompatibility complexes (MHCs), proteins that help distinguish between self and nonself in the body.9 A proper HLA match is dependent on the ethnicities of both the donor and recipient, as individuals from varying regions have HLAs that have adapted to selective pressures in their respective environments.4,8 For example, many generations of individuals in Africa survived Malaria and have been found to have HLA-C*06:02, which is associated with Malaria resistance.4 Due to this, finding donor matches for bone marrow transplants can be difficult for those with a mixed ethnic background.4,8
In addition, the donor cells in a bone marrow transplant are also more immunologically developed, meaning that they have been exposed to antigens or foreign substances that trigger an immune response. As such, eligible donors must be at least 16 years old.2, 6 In contrast, cord blood transplants offer the possibility for patients requiring a stem cell transplant to find a closer match. Umbilical cord blood cells are more immunologically naive compared to bone marrow samples. This is a benefit, as patients undergoing transplants sourced from umbilical cord blood have a lower chance of rejecting the foreign blood.6 Preventing transplant rejection can reduce the chances of suffering more severe complications such as Graft-vs-host disease (GVHD).6
GVHD is a condition in which the immune cells from transplanted cells view the tissues of the recipient as foreign and attack the transplant recipient’s body as a result.9 Early on, the immune system of an individual is conditioned to be able to identify and differentiate between self and nonself cells with the help of major histocompatibility complexes (MHCs).9 There are two classes of MHC proteins: class I, which is expressed on all nucleated cells in the body, and class II, which is only present on antigen-presenting cells (APCs), such as B-cells, dendritic cells, and macrophages.9
The pathogenesis of GVHD can be broken down into 3 major phases, known as Phase 1, 2, and 3.5 Phase 1 is marked by an increased expression of inflammatory cytokines, which occurs when tissue damage is present in the body. This release of inflammatory cytokines is usually the result of damage occurring at the molecular level, such as chemotherapy and radiation therapy.10 Chemo and radiation therapy are used to first kill abnormal blood cells contributing to the blood disorder in question.9 This amplifies the activity of APCs of the recipient, increasing the likelihood of activating foreign T-cells from the transplant.
Phase 2 begins when T-cells from the donor identify the recipient’s cells as APCs and become activated, secreting more inflammatory cytokines to create a positive feedback loop.9 Finally, Phase 3 is when natural killer cells (NK cells) and cytotoxic T-cells attack the organs and tissue of the transplant recipient.9 With the umbilical cord blood transplants and the naive T-cells it contains, the chance of GVHD is reduced.
However, the umbilical cord blood transplant is not without its shortcomings. The yield of stem cells per umbilical cord blood unit is low, and a sample must be at least 40 mL.12 Approximately only 12% of these units have enough stem cell content to treat a person weighing roughly 176 lbs, or 80 kg.12 To troubleshoot this drawback, there are instances in which more than one type of umbilical cord unit can be used as a combined treatment (derived from more than one donor). Another issue is that new parents are often not educated on the cord blood banking process.11 Without knowing what use umbilical cord blood can serve, families might unwittingly waste this tissue. As a result, this limits the supply of cord blood samples available for use.11 However, with the help of healthcare providers and better access to educational resources, families can be more thoroughly supported in their decisions.
To improve cord blood transplants, physicians must educate and encourage those with eligible umbilical cord blood to donate. This expands the pool of potential matches for patients needing treatment, particularly those who could not find a full match for procedures like bone marrow transplants.9 Hopefully, with more resources to better educate the community on umbilical cord blood transplants, we can better use what is otherwise disposed of to potentially save more lives.
References:
1. Badowski, M. S., & Harris, D. T. (2012). Collection, Processing, and Banking of Umbilical Cord Blood Stem Cells for Transplantation and Regenerative Medicine. Methods in Molecular Biology, 279–290. https://doi.org/10.1007/978-1-61779-815-3_16
2. Ballen, K. (2017). Update on umbilical cord blood transplantation. F1000Research, 6, 1556. https://doi.org/10.12688/f1000research.11952.1
3. Bhandari, J., Thada, P. K., & Puckett, Y. (2020). Fanconi Anemia. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559133/
4. Bolon, Y.-T., & Madbouly, A. (2024). Race, ethnicity, ancestry, and aspects that impact HLA data and matching for transplant. Frontiers in Genetics, 15. https://doi.org/10.3389/fgene.2024.1375352
5. Cooke, K. R., Luznik, L., Sarantopoulos, S., Hakim, F. T., Jagasia, M., Fowler, D. H., van den Brink, M. R. M., Hansen, J. A., Parkman, R., Miklos, D. B., Martin, P. J., Paczesny, S., Vogelsang, G., Pavletic, S., Ritz, J., Schultz, K. R., & Blazar, B. R. (2017). The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, 23(2), 211–234. https://doi.org/10.1016/j.bbmt.2016.09.023
6. Field, M. J., Lawrence, R. L., & Zwanziger, L. (2015). Immunosuppressive Drugs for Transplant Patients. Nih.gov; National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK225251/
7. Gluckman, E., & Rocha, V. (2005). History of the clinical use of umbilical cord blood hematopoietic cells. Cytotherapy, 7(3), 219–227. https://doi.org/10.1080/14653240510027136
8. Gragert, L., Eapen, M., Williams, E., Freeman, J., Spellman, S., Baitty, R., Hartzman, R., Rizzo, J. D., Horowitz, M., Confer, D., & Maiers, M. (2014). HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry. New England Journal of Medicine, 371(4), 339–348. https://doi.org/10.1056/nejmsa1311707
9. Justiz Vaillant, A. A., & Mohammadi, O. (2020). Graft Versus Host Disease. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK538235/
10. Markey, K. A., MacDonald, K. P. A., & Hill, G. R. (2014). The biology of graft-versus-host disease: experimental systems instructing clinical practice. Blood, 124(3), 354–362. https://doi.org/10.1182/blood-2014-02-514745
11. Renece Waller-Wise. (2022). Umbilical Cord Blood Banking: An Update For Childbirth Educators. PubMed, 31(4), 199–205. https://doi.org/10.1891/jpe-2021-0006
12. Umbilical Cord Blood Banking. (2023, December). Www.acog.org. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2019/03/umbilical-cord-blood-banking
Image References:
1. NHS. (2019). What is cord blood? Cord Blood Bank – NHS Blood and Transplant. https://www.nhsbt.nhs.uk/cord-blood-bank/what-is-cord-blood/