INTRODUCTION:

Umbilical cord blood (UCB) was once considered a waste product and was discarded with the placenta after delivery. With advances in the field of medical sciences, it has been found to be a rich source of life-saving hematopoietic stem cells and has saved many lives in the recent decades. Human Leucocyte Antigen (HLA) matching is required to prevent rejection and other transplant related complications in receipient. HLA matched donors can potentially save patients from serious illnesses like malignancies, storage diseases and hematological disorders, but may not be available for the majority of suffering patients. With advances in cord blood transplantation, many such patients are now able to find a fully or partially HLA-matched cord blood donor.

Various centers across the world are performing cord blood stem cell transplantation for a variety of genetic, hematologic, immunologic, metabolic, and oncologic disorders. On the other hand, a number of private cord blood banks have been established in the recent years that encourage parents to bank and insure their children’s UCB for autologous use or for directed donor allogeneic use for a family member. This article discusses the recommendations of the Indian Academy of Pediatrics (IAP) regarding the indications and benefits for storing the UCB in public or private banks based on the expert panel recommendations and the review of the scientific literature¹.

Characteristics of Umbilical Cord Stem Cells:

Stem cells are the next frontier in medicine. Stem cells are thought to have great therapeutic and biotechnological potential. This will not only to replace damaged or dysfunctional cells, but also rescue them and/or deliver therapeutic proteins after they have been engineered to do so. Currently, ethical and scientific issues surround both embryonic and fetal stem cells and hinder their widespread implementation. In contrast, stem cells recovered postnatally from the umbilical cord, including the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells, are a readily available and inexpensive source of cells that are capable of forming many different cell types (i.e., they are “multipotent”)². Umbilical cord blood (UCB) collected from the umbilical cord differs from the peripheral blood in its properties. It is a rich source of hematopoietic stem cells, which have the properties of self-renewal as well as the ability to differentiate into myeloid and lymphoid cell lineages. DNA in these cells has a longer telomere length, which helps in long time hematopoiesis. The cord blood is also a rich source of mesenchymal cells, which are known to suppress the response of Graft-versus-host disease (GVHD) and has naïve T cells with minimal recognition of foreign antigen. These properties of cord blood cells have been successfully exploited in the treatment of various malignant, hematological and storage disorders by using UCB as a source of stem cells in HSCT. UCB can be cryo-preserved and stored for more than 15 years¹.

Umbilical Cord Blood Banking:

UCB can be collected from the placenta during the third stage of labor (after delivery of baby) or after the delivery of placenta. This process does not pose any risk to the baby or mother. UCB is collected from the umbilical vein into a sterile closed system collection bag containing an anticoagulant solution. Blood from placenta flows through the cord by gravity into the collection bag which is placed lower. Then the bag is transported to the cord blood bank, where it is tested, processed and cryopreserved. The entire procedure must be performed by properly trained and qualified personnel in a well equipped laboratory to minimize microbial contamination of the unit and loss of viability of the stem cells. After thawing, this product can be transplanted into a host after they have received conditioning/ preparative regimen for transplant. As the stem cell count of the product is correlated with the outcome of future transplantation, it might be tempting for the bankers to increase the product volume by early cord clamping to collect more cord blood. However, this is an unethical practice as delayed cord clamping has a positive effect on the hematological status of the infant. Hence, cord blood collection should not change the routine practice of umbilical cord clamping. Also, cord blood collection is not advisable in complicated deliveries like twin gestation and prematurity³.

Umbilical Cord Blood Transplantation (UCBT):

Using UCB as a source of transplantable hematopoietic stem (HSC) and progenitor (HPC) cells was suggested by Hal Broxmeyer in a private meeting with the late Edward A. Once it was decided to attempt a UCBT, FA was selected as a first disease to treat, because HLA-matched sibling donor BMT was a treatment option for FA and in families who had affected children with FA, there was the possibility of using BM from nonaffected siblings who were an HLA match for the affected child. The first UCBT was done in Paris, as Gluckman had the best clinical results at that time using BMT to treat patients with FA The UCB cells were infused into the conditioned recipient without separation or washing to ensure little or no loss of these precious cells. Later studies demonstrated volume-reduced UCB units were acceptable for UCBT.

Only 25-30% of patients who require allogenic HSCT can find an HLA-matched sibling donor. UCB serves as an alternative stem cell source. In October 1988, Gluckman performed the first UCBT in a 5-year-old child with Fanconi anemia, who remains in complete hematological and immunological reconstitution for more than 25 years. Initially, UCBT was performed only in children weighing up to 10-15 kg, as the low number of stem cells in a single unit was thought to be insufficient for older children and adults. Nowadays, it is used increasingly even in adults, using double umbilical cord blood units. The advantages of using UCB are that it is readily available and it can be transplanted across HLA barriers⁴.

Public versus private cord blood banking:

The first publicly funded cord blood bank was established in New York in 1993. Cord blood units stored in public banks are available for the patients in need. The donors are not charged for the storage process. The recipients who will be using the cord blood units for their treatment will be charged ⁵.

In a private bank, UCB is stored privately for a particular family which opts for cord blood storage, and can be utilized by the family as the need arise. The likelihood that they will ever be used is remote (range of available estimates is from 1:1000 to 1:200 000). The family will be charged for the storage process. The number of cord blood units stored in private banks far exceeds that stored in international stem cell registries for public use, and is three times more than that in public banks.

This deprives a patient in need of an HSCT from a potentially life-saving UCB unit, as cord blood units stored in private banks are not available for the general population¹.

Facts and myths of private cord blood banking:

The young and expecting parents, who are anxious, are vulnerable to the emotional marketing of the private cord blood banks. Parents’ sense of obligation towards their own children is exploited in this field. The fact is that these autologous cord stem cells (one’s own stem cells) cannot be used to cure genetic disorders (including hemoglobinopathies, storage disorders, etc.) as these cord stem cells harbor the same genetic mutation, resulting in disease. Also, in hematological malignancies, allogenic stem cells are preferred over autologous stem cells due to the proven therapeutic effect of graft-versus leukemia reaction, which occurs only in allogenic transplantation. However, even if such indication arises, stem cells can readily be harvested from the peripheral blood or bone marrow of the patient, which provide

similar results to that using UCB. Private banking is highly recommended when there is an existing family member (sibling or biological parents only) suffering from a condition approved to be cured by allogenic stem cell transplantation like leukemia, hemoglobinopathy, bone marrow failure, etc. (directed

donor cord blood collection). Thalassemia is a common non-malignant indication for HSCT in India. Promotional advertisements by private cord blood banks are often misleading for the public. In countries like France and Italy, private cord blood banking and any form of advertisement regarding this is illegal¹.

Indian Perspective:

India, being the second most populous country, possesses a great potential in the field of cord blood banking. Unfortunately, private cord blood banking has been projected as a form of ‘biological insurance’. In India, there are four public blood banks and more than five private cord blood banks that are functional at present. Public cord banking is the need of the hour, yet has not flourished in our country. Another fact is the lack of awareness regarding the utility of cord stem cells and its uses among the general population as well as the medical personnel including the pediatricians and obstetricians, who will be approached by parents opting for cord blood storage in private or public banks.

IAP CONSENSUS FOR CORD BLOOD BANKING IN INDIA

1. Umbilical cord blood is a rich source of hematopoietic stem cells, which have been successfully used for curing various conditions including malignancies, hematological conditions, primary immunodeficiency and few selected inherited metabolic disorders.

2. Umbilical cord blood can be safely collected from the placenta without any risks to the baby and the mother in an otherwise uncomplicated delivery.

3. Cord blood collection is not advisable in complicated deliveries.

4. Public cord blood banking serves the actual purpose of preservation, which provides cord blood stem cells for the patients lacking matched sibling donor or matched unrelated donors, in need of hematopoietic stem cell transplant.

5. Autologous cord blood stored privately cannot be used for treating one’s own genetic conditions in future (including hemoglobinopathies, storage disorders, hemophagocytic lymphohistiocytosis, immunodeficiencies, etc.) as the cord stem cells harbor the genetic abnormality leading to the disease.

6. Autologous cord blood is not preferred in treating various hematological malignancies, due to proven therapeutic effect of graft-versus-leukemia reaction seen only in allogenic stem cell transplantation.

7. Cord blood storage is not indicated for autologous stem cell transplantation.

8. Public cord blood banking should be promoted, which expands treatment options for patients suffering from certain serious illnesses.

9. India, with high birth rate and diverse genetic pool, has a bright prospect in public cord blood banking to increase the chances of finding HLA-matched hematopoietic stem cells for transplant.

10. Private cord blood banking is not a ‘biological insurance’ and its role in regenerative medicine is still hypothetical.

11. Private cord blood banking is recommended only if there is an existing family member (siblings or biological parents only), who is currently suffering from diseases approved to be benefitted by allogenic stem cell transplantation.

12. It is imperative to spread awareness about myths and facts about cord blood banking (public and private) among the public (by mass campaigning) and among the health workers (by including this subject in under graduate academic curriculum).

13. Advertisements for private cord blood banking by companies (e.g., by using celebrities) are often misleading and exploit parents’ emotions for profit, at the vulnerable period of pregnancy¹.

Recommendations of International Societies:

American Academy of Pediatrics recommends preferring public UCB banks. Role of private banking is limited and are not subjected to strict regulatory oversight and may be of lesser quality. Parents should be informed about the potential benefits and limitations of autologous cord cells and the lack of scientific data in its use in regenerative medicine. Regulatory agencies have to ensure that the cord blood banking programs comply with accreditation standards. American Society for Blood and Marrow Transplantation encourages public UCB banking, as the probability for using one’s own cord blood is very small (0.04 to 0.0005%) . Society of Obstetricians and Gynaecologists of Canada suggests that there is minimal harm to the mother or newborn with UCB banking if priority is given to maternal/newborn safety during childbirth and collection should not interfere with delayed cord clamping. Unbiased information about UCB banking options should be provided to pregnant women prior to the onset of active labor, ideally during the third trimester, with ample time to address any questions ¹.

Since the publication of the previous AAP policy statement on cord blood banking, 2 several other professional societies have issued similar statements. The American Society for Blood and Marrow Transplantation’s view is that donation of cord blood to the public is preferable because the use of cord blood stored in private cord blood banks for therapy rarely occurs. European countries have advocated for the adoption of strict guidelines regarding public collection and use of cord blood for transplant in the case of life-threatening illnesses ⁷.

CONCLUSION:

Policymakers should promote public cord blood banking. The myths and lack of awareness regarding cord blood banking among health care professionals and the public is a big threat leading to exploitation by private banking. The narrow indications of the possible utility of the baby’s cord blood stored privately should be highlighted to the family opting for cord blood banking.

REFERENCES:

1. Sachdeva A. Gunasekaran et al. Umbilical cord blood banking: Consensus statement from Indian academy of pediatrics. Available from Url: https://www.indianpediatrics.net/june2018/489.pdf

2. Mark L. Weiss, Deryl L. Troyer. Stem cells in Umbilical Cord. 2006; 2(2): 155–162. Available from Url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753204/

3. Cord blood banking: Cryo cell international. Available from Url: https://www.cryo-cell.com/cord-blood-banking

4. Karen K. Ballen,Eliane Gluckman, and Hal E. Broxmeyer.Umbilical cord blood transplantation: the first 25 years and beyond. Available from Url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952633/

5. Shearer WT, et al. Pediatrics. 2017. Available from Url: https://www.healio.com/pediatrics/practice-management/news/online/%7Bce40579e-7dc7-45ea-8aa5-2a31d8bec345%7D/aap-stresses-value-of-public-vs-private-cord-blood-banks

6. Cord Blood Myths and Facts. Available from Url: https://www.cb-association.org/myths-and-facts

7. William T. Shearer. Cord Blood Banking for Potential Future Transplantation. Available from Url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091883/

Received on 13.01.2020 Modified on 10.02.2020

Int. J. of Advances in Nur. Management. 2020; 8(2):165-168.

DOI: 10.5958/2454-2652.2020.00039.6