Abstract
This review summarizes biobanks of umbilical cord blood (UCB), beginning with a series of crucial experiments to build the technology to treat hematological diseases. UCB is used as an alternative source of hematopoietic stem cells in the treatment of patients with hematological malignancies, bone marrow failure, and inherited metabolic abnormalities. In this review, we evaluate the procedures for collecting, processing, and storing cord blood and discuss the advantages and disadvantages of current applications in regenerative medicine, particularly for hematological disorders in Vietnam. Our analysis compares cord blood banks, including private and public banks, in Vietnam and worldwide. An integrative overview of UCB transplantation in patients with different diseases and the degree of patient adaptation is analyzed. This review concludes with an assessment of the impact of measures taken to combat the COVID-19 pandemic on the banking of autologous cord blood and cord tissue in Vietnam compared to other banks in the world. National policies in the fight against a pandemic may differ from the global level. Human behavior, access to medical treatment, number of health professionals, health facility infrastructure, and timing of response in different cultures contribute to these differences.
Introduction
Umbilical cord blood (UCB) is the blood in the umbilical cord tissue, which is 10–50 cm long and lies behind the placenta, allowing the exchange of gas and nutrients between mother and child until the time of birth. The average volume of UCB collected from the umbilical vein ranges from 50 to 200 mL and varies from person to person. UCB units are processed if the period between collection and cryopreservation is less than 48 hours and the sample is greater than or equal to ≥50 mL.1,2
As one of the multipotent stem cells, 3 hematopoietic stem cells (HSCs) can give rise to whole blood cell lineages throughout the human lifespan, primarily because of their maintenance, self-renewal, and differentiation, which are crucial for living organisms. 4 Research into the existence of HSCs in UCB has changed from a traditional throwaway to a valuable commodity. Remarkably, UCB has shown a higher proportion of more primitive HSCs and a better expansion potential than adult bone marrow. The authors pointed out that mesenchymal stem cells (MSCs) in UCB have a higher proliferative capacity, in contrast to bone marrow MSCs.5–7 As a result, the establishment of cord blood banking has rapidly developed and spread with technological advances and high-quality infrastructure for collection, storage, and transplantation. 8 Ende et al. performed the first case of in vivo UCB transplantation in 1972, 9 but the results were not conclusive. It was not until 1988 that Elianne Gluckman and her partners in Paris performed UCB transplantation of a human leukocyte (HLA)-identical sibling in a patient with Fanconi anemia, and the results were successful. 10 Subsequently, researchers have expanded the applications of leukocyte transplantation for treating hematological malignancies, bone marrow failure, and inherited metabolic diseases. By 2016, there were 30,000 cases of leukocyte transplantation worldwide. 11
In August 1999, the Ho Chi Minh City Blood Transfusion and Hematology Hospital opened the first UCB Public Bank in Vietnam. For 20 years, there have been over 10 UCB banks in Vietnam, which can store about 20,000 UCB samples. In 2014, Vinmec Tissue Bank established the first private UCB bank in Vietnam, which is the most developed and modern bank. So far, Vinmec Tissue Bank has stored about 7,000 UCB samples and performed five transplants for patients with diseases such as thalassemia, Asperger’s syndrome, and cerebral palsy. Although cord blood banking is becoming more and more popular as a way to preserve “living medicine”, unfortunately, it has not yet received the attention it deserves from Vietnamese society due to its high cost, the need for technology and highly skilled medical staff during the treatment process. Addressing this issue is crucial for parents who have likely been misinformed about stem cell banking, and especially for most pregnant women who may want to bank cord blood, but do not have sufficient information.12–14
In 1993, the first public UCB bank was established and operated in New York. 15 Subsequently, UCB opened several national public banks in the 1990s, starting with the United States, France, the United Kingdom, Germany, Italy, and Spain. 10 A recent data analysis found that in 2020, there were over 450 UCB banks in 97 countries around the world, including private and public banks, holding about 5 million UCB shares. Compared with 2016, there were only 207 private cord blood banks (CBBs) in 54 countries and 158 international public CBBs in 36 countries, with over 73,1000 units of UCB. 16 After 4 years, the number of established UCB banks has increased significantly, indicating a substantial rise in the demand for cord blood storage as a form of biological insurance and for clinical applications. UCB bank implements a thorough process from collecting, processing to freezing cord blood immediately after the baby is born. In this procedure, it is essential to follow established and tested standard protocols strictly to measure the quality and quantity of biological samples of cord blood. In the past, cord blood was a medical waste that was disposed of after birth. Over three decades, after the first successful transplantation of stem cells from cord blood, cord blood has become a ubiquitous source of primitive HSCs. Because of increasing evidence of their safety, efficacy, and reduced risk of surgical complications, UCB banks are being perceived by the public and medical professionals as an alternative transplant source instead of bone marrow transplantation (BMT). Thus, CBBs are assuming an increasingly important position in the treatment of patients with hematological diseases and genetic disorders, diagnosed with the system of processing and cryopreservation of cord blood units (CBUs). More and more parents are inquiring about detailed information and making the conscious decision to keep their neonatal UCB private as a kind of “biological insurance” for later use, while voluntarily contributing to a public bank when unnecessary. This article provides an overview of the history, present state, and future potential of UCB banking in the Vietnamese community. We also present the progress of CBBs in Vietnam and discuss other aspects of UCB, including ethical issues, criteria for CBBs, potential clinical applications, and future challenges.
Historical Perspectives
In the 1970s, many scientists showed the potential of UBC containing many immune system precursor cells, such as granulocytes and macrophages, by culturing them in vitro. Cryopreservation was used to freeze these blood units from the placenta, ushering in the era of stem cells. 3 In 1972, stem cell transplantation from umbilical cord blood was considered a new method. 9 However, it was in 1989 that Gluckman and her colleagues reported the first successful umbilical cord blood transplant on a 5-year-old boy with Fanconi anemia (FA) at Saint-Louis Hospital in Paris. 10 In 1993, Dr. Joanne Kurtzberg and her team at Duke University conducted the first successful unrelated cord blood transplant for a 4-year-old boy with Tcell leukemia. Over the following 2 years, Dr. Kurtzberg and her team at Duke University performed 25 additional transplants, establishing cord blood as a viable and valuable resource for patients who could not find a related or unrelated donor for transplantation. 12 This ushered in a new era of stem cell transplantation.
Because of the proliferation of medical facilities, the scope of cord blood transplantation (CBT) and banking expanded rapidly. In 1992, Dr. Pablo Rubinstein founded the New York Blood Center, the first and one of the largest public blood banks in the world,17,18 which then led to the establishment of several blood banks around the world, for example, in Milan, Paris, Dusseldorf, and Sydney.19–21 In 1998, the National Marrow Donor Program established the UCB program and established the Center for Cord Blood, which now includes 21 CBBs in the United States and three international CBBs. 17 In December 2005, Congress passed the Stem Cell Therapeutic and Research Act (Stem Cell Act 2005), Public Law 109–129. 22 The C.W. Bill Young Cell Transplantation Program helps patients find suitable HSCs from accepted donations, especially for untreated blood disorders.
Options for Cord Blood Banking
After the potential of UCB was recognized, intense competition has developed between family banks with and without direct banking. Since their inception, CBBs have had two major categories: public and private CBBs. Public CBBs are nonprofit organizations funded by the government to provide an available source of altruistic UCB donations for any patient in need of an HLA-equivalent match. Still, there is no assurance that CBUs will be available to donors and their families in the future. Although CBUs are used for transplantation, communication between donor and recipient is virtually nonexistent. 23 Unlike a public bank, a private CBB or family bank is for profit management, whose purpose is to collect and store processed CBUs for family members. The CBB or family bank collects a fee to ensure the longevity of the CBUs, and the child’s mother possesses the legal ownership of the stock of CBUs. Therefore, accessibility between the CBUs and their owners is exclusively ratified. Apart from the difference in ownership of CBUs, the main difference between private CBUs and nonmanaged CBUs is that private CBUs charge a fee for medical services before carrying out the collection, processing, and storage of the UCB of the newborn for the private use of family members. 13 The cost of storage varies widely between regions, countries, and private CBBs.24,25
In Vietnam, there are two types of CBBs: public banks and private banks, each serving distinct purposes and catering to different needs within the medical and research communities.26–29 People who can use cord blood samples when using services at private banks include people from the baby’s own family. Baby’s own cord blood is always a 100% match for the baby, making an autologous transplant or infusion, the preferred method for treating many conditions because the risk of graft-versus-host disease is minimal. 29 Siblings from the same parents have a 75% chance of being a perfect or partial match (25% chance of being a perfect match and a 50% chance of being a partial match) and another one-in-four chance of not being a match at all. Each parent gives one HLA group (haplotype) to their baby, so half the HLA markers come from the mother and half from the father. This means the child’s cord blood is always a 50% match for either parent. By the slight chance that the parents share HLA markers, the number of matching HLA markers between the child’s cord blood and his or her parents could increase beyond 50%. Even though parents are not usually more than a 50% match, they can undergo a haploidentical transplant using the baby’s cord blood.27,29 CBBs recognizably flourish in developed nations where the standard of living is far above average. Vietnam is a developing populous country in Southeast Asia with an estimated population of over 90 million. Figure 1 shows the history of CBBs in Vietnam. Despite remaining shortcomings in terms of economic conditions and limited rationality, there are some crucial milestones, especially in cord blood banking. In 2001, doctors at the Ho Chi Minh City Blood Transfusion and Hematology Center successfully performed a transplant on a patient with ALL. 29 This success provided the impetus for the next transplants and the establishment of CBT centers and CBBs. There are now nine sites capable of performing HSC transplants and eight banking centers (Table 1).

The history of cord blood banks in Vietnam.
Specifications of CBBs and UCB Bank in Vietnam
Has been Association for the Advancement of Blood & Biotherapies (AABB) accredited (https://www.aabb.org/standards-accreditation/accreditation/accredited-facilities/cellular-therapy-facilities).
The cost is about one year for one newborn baby. The first year includes collection, processing, and storage.
CBB, cord blood bank; UCB, umbilical cord blood; N/A, not applicable; N/I, no information.
Collection
The collection of UCB in term births occurs either in utero or ex utero. In utero, a trained specialist collects cord blood from the placenta during the third stage of labor before delivery. The technical procedures for the collection of cord blood at Vinmec Tissue Bank follow these strict rules: After confirming the information and collecting 15 mL of venous blood from the mother for screening tests, the trained specialists prepare and disinfect the equipment (with cesarean section, they wear sterile clothes). After delivering the baby, the doctors/nurses must clamp the umbilical cord with two sterile scissor clamps and cut the cord between the two clamps. Collectors immediately receive the clamped umbilical cord and disinfect it at least two times with Betadine gauze or Chloraprep swabs (vaginal delivery only). Collectors will identify the umbilical cord vein, then insert the needle into the umbilical cord vein at a point near the needle holder (the blood bag is placed on Steri-Quick). The blood flows from the placenta into the blood bag, providing a volume of 250 mL, including anticoagulant (CPDA1) in the bag, under gravity. Collectors wait 2–5 minutes for the cord blood to flow completely into the bag, remove the needle, close the cap carefully, tie off 1–2 knobs of cord blood, and finish the procedure. The volume of collected cord blood must be over 60 mL, including anticoagulant (equivalent to approximately 100 g of bag including collected blood), to ensure the quality of the following processing and storage process (Fig. 2).

The process of collecting cord blood.
Compared with in utero and ex utero collection, the risks to the mother and newborn are lower with ex utero collection, but the rate of microbial contamination are reported to be higher. However, some studies have shown that the volumes of UCB collected and the rate of contamination are not significantly different when trained professionals measure the procedure using either method. 42 Furthermore, UCB in utero can be collected in combination with ex utero in a special situation, and this is called mixed sites. Each UCB bank sets the values for the total number of nucleated cells (TNCs) per unit of cord blood differently to ensure quality requirements for storage and transplantation. However, some data analyses show that TNCs play a crucial role in the success of transplantation. Therefore, the requirements for TNC quantity per CBU has increased in most CBBs in the world in recent years. 8 In public banks, the ideal number of TNCs per UCB unit is over 1 × 109, whereas most private banks require a lower number of over 3 × 108 TNCs per UCB unit. 43 Some scholars are skeptical that the number of TNCs per UCB unit in private banks is insufficient to meet the demand for transplantation, while private banks present much evidence of successful provision of TNCs for transplantation in their centers. At Vinmec Tissue Bank, the acceptable rate of TNCs per UCB unit is over 5 × 108 TNCs per UCB unit and cell viability is over 85%.44,45 Vinmec Tissue Bank collected and preserved 760 UCB units in 2022 and 295 UCB units in 2023 for customers at Vinmec Times City International Hospital.
Previously, UCB banks had to provide too much space and infrastructure for storing CBUs because it was collected and preserved.46,47 Therefore, scientists have researched and figured out the standard for processing cord blood that can remove the red blood cells and plasma, while preserving the number of stem cells for transplantation. Importantly, this procedure is followed strictly to preserve maximum TNCs and CD34+ myeloid progenitor cells in the stored buffy coat layer after discarding the nonessential components.46,48 The figure below shows the description of the collection (Fig. 2).
Processing
In the early years of UCB development, the degree of quality deterioration due to the time between collection and processing was not presented. Experts considered whether a longer period affected the quality of stem cells. 48 The method using stem cell extraction from UCB is shown in Figure 3. Conventional UCB should be processed within 48 hours of collection and primarily within 24 hours to measure the highest viability of cells. At Vinmec Tissue Bank, the processing procedure is specifically designed for the trained specialist (Fig. 4).

Method using stem cell extraction from umbilical cord blood.

The processing procedure is specifically designed for the trained specialists at Vinmec Tissue Bank.
The purpose of this processing is to eliminate red blood cells, plasma, and nonessential components during the storage process of cord blood, while maintaining a maximum number of white blood cells (WBCs), TNCs, and CD34+ cells in the stored buffy coat layer with a defined volume of 20–25 mL. 37 This product is mixed with a storage solution of Dimethyl Sulfoxide (DMSO) + dextran to preserve the structure and function of the cells during freezing and to support transplantation for the treatment of blood disorders or stem cell-related diseases in the future. Before cryopreserving each umbilical cord blood unit in liquid nitrogen (−196°C), processed units will be counted for CD34+ stem cells using Stem Kit Reagent and flow cytometry. 37 This test provides data on the viability of stem cells (%), CD45+ WBCs, and CD34+ HSCs. According to FDA guidelines for umbilical cord blood stem cell products licensed for cell therapy for unrelated individuals, the minimum acceptance criteria for a stem cell unit at a community bank should include the following: no evidence of microbial contamination and TNC count, viable CD34+ cell number, cell viability, and identity (HLA, ABO/Rh) that matches the recipient.
In 1999, the OptiPress was introduced as the first semiautomatic volume reduction system in UCB processing. During the 20 years of development, automated systems such as SEPAX 540 (Biosafe SA, Eysins, Switzerland) or AutoXpress were used instead. 49 At Vinmec Tissue Bank, we use the most advanced equipment and technologies for processing. AutoXpress platform (AXP) automated cord blood processing is an approach that uses a separation system and a special kit to collect a maximum number of nucleated cells and ensure asepsis during the processing process, reducing the risk caused by human factors. After collection, the cord blood sample is transferred to the AXP system for automated processing. 37 Then different centrifugation methods are used with different speeds and times to remove red blood cells, plasma, and other unnecessary components. The total volume of the UCB bag before processing is 60–200 mL. After processing, the red cells and plasma are discarded. Only 20–25 mL of stem cells remain, which are mixed with a solution of 10% DMSO + 10% dextran to preserve them.
Storage
After processing, the cord blood sample is frozen to “lock” metabolism and cell activity and ensures a cell life of more than 25 years. The cord blood samples must be frozen by an automated process with a slowly decreasing temperature to avoid thermal shock and the formation of cellular ice crystals. In the next step, the cord blood samples are automatically brought to deep subzero temperatures. At Vinmec, UCB samples are cryopreserved in liquid nitrogen (−196°C) in the Bioarchive system using rate-controlled automatic hypothermia. All samples stored in the Vinmec Tissue Bank must undergo screening tests for infectious diseases, ABO Rh type, and HLA type. If infectious diseases are detected, the storage of UCB specimens must be carefully reviewed. UCB standard protocols for cryopreservation require that an average of 80% TNCs and >90% CD34+ myeloid progenitor cells must remain in the final sample after processing. 50
Clinical Studies
In the past, UCB was mainly used to treat hematological malignancies. The first transplantation of UCB was performed by Arleen Auerbach (Rockefeller College in New York) and Gluckman (Hospital Saint Louis in Paris) in October 1988. They used the UCB unit taken from a female baby at birth to transplant her brother with FA.51,52 The French ethics committee approved the performance of this first transplant with UCB, which was considered an emergency source of treatment at the time. The recipient patient was five years old and suffered from severe aplastic anemia due to FA. After transplantation, the result was positive that the patient did not have graft-versus-host disease (GVHD) and was currently in long-term hematological health. The donor also has complete immunological reconstitution 25 years after UCB transplantation. 52 This successful transplant opened the development for the use of UCB to treat diseases in the future. In the 21st century, the number of diseases that can be treated with UCB has increased dramatically, such as immunodeficiencies, bone marrow failure syndromes, hemoglobinopathies, blood disorders, cancers, and metabolic disorders (Fig. 5).

Cord blood stem cell applications.
Dealing with ethical issues involving all aspects of public and private CBBs is always an obstacle for both managers and users. In private CBBs, many questions arise about the problem of whether obstetricians have sufficient authority to negotiate with parents whether they consent to the removal and retention of their baby’s data CBB. 13 Must obstetricians and birth attendants be responsible for conveying information and the purpose of private CBBs to clients? Fox and his colleagues argue that obstetricians must inform clients of the limited benefits of family-led CBBs, highlighting solutions to limited sample supplies for urgent need for transplants. 53 They received agreement from Herlihy and Delpapa, who suggest that the profession should be accountable to the mother and the newborn to offer full options to guarantee their best personal decision. 54 In Vietnam, the idea of UCB banking is not abandoned, unlike some African countries such as Nigeria because of Indigenous religion and historical belief in allogeneic tissue transplantation. 37
In the past 10 years, stem cell transplantation for treating hematology and cancer patients in Vietnam has advanced significantly, with improvements in techniques and the establishment of new transplant centers. In 2019, the Hanoi National Institute of Hematology and Blood Transfusion announced that it had performed 400 HSC transplants since the technology was introduced 13 years prior, making it the largest stem cell transplant unit in Vietnam. 28 As of November 2023, the Ho Chi Minh Blood Transfusion and Hematology Hospital’s one-year transplant report showed that the number of patients receiving stem cell transplants was 80, an increase of 20 from the previous year. The hospital also supports several places such as Children’s Hospital 2, Oncology Hospital in Vietnam, in training and transferring stem cell transplant techniques. 29
SARS-CoV-2/COVID-19 to Cord Blood Banking
COVID-19 has affected many areas, including food production, the economy, import–export, and health facilities. The decrease in demand for cord blood unit storage is attributed to concerns about potential transmission of COVID-19 and the lack of collection methods for infected individuals.55,56 However, some researchers have shown that vertical transmission of COVID-19 seems rare and unnecessary for screening and the incidence of COVID-19 in neonates was thus uncommon, and it was seldom symptomatic.57–59 The infection rate did not increase when the baby was born vaginally, breastfed, or allowed contact with the mother at Vietnam and in the world. The total number of UCB units collected, processed, and stored by Vinmec Tissue Bank in the first 3 months of 2023 decreased slightly from 175 to 168 compared to 2022 due to the impact of the COVID-19 pandemic.
Although the impact on the number of stored UCB units is minor, transporting UCB in Vietnam has become more difficult. There have been two cases where UCBs have been canceled due to flight disruptions. However, patients can collect their tissue samples for transplantation at the Vinmec Tissue Bank even during a pandemic. In some countries around the world, they report the same situation as the Vinmec Tissue Bank in Vietnam. At the Cleveland Cord Blood Centre in Ohio, USA, the number and productivity of UCB units collected in 2019 remained in the normal range, although sample collection had to be stopped at one site. Seven units of UCB had to be discarded due to flight disruptions. However, it is worth noting that there was no impact on the umbilical CBUs shipped from this bank for transplantation. 60 AusCord Bank Australia compared the number of UCB units requested for transplantation for Australian or international cases in the 5 months from 1 January to 30 June between 2019 and 2020. 61 The results indicate an increased awareness of UCB, particularly among Australian patients. It highlights the importance of UCB in treating disease, particularly in global emergencies, such as the COVID-19 pandemic. UCB units were available to be provided by AusCord Bank for patients against the effects of the pandemic.
Future Developments
As the world population continues to grow, suitable stem cells for transplantation are no longer abundant, especially as the need for CBT increases. 62 Public CBBs can take advantage of the abundance of funding to build a large stock of high-quality, transplantable CBUs, especially considering many studies describing attempts to optimize HLA matching units between donor and recipient. Many countries should align their strategies to reduce the high cost of storage and transplantation, providing a better alternative to chemotherapy or radiation, which are commonly used treatments.
In Vietnam, despite the promising potential of CBBs, several challenges loom, which could impede the development and widespread adoption of biobank in the country. Some UCB banks in Vietnam do not have a process of obtaining quality assessment certificates from international organizations and may pose challenges in maintaining consistency and quality across different biobanks (Table 1). Without standardized practices, there is a risk of variability in sample quality and efficacy, potentially compromising the outcomes of stem cell transplantation and research endeavors. 63 Establishing and maintaining CBBs entail significant financial investments in infrastructure, equipment, staffing, and ongoing operational expenses. Securing adequate financial support and sustainable funding mechanisms to cover these costs can be a hurdle, particularly in a country that has a developing economy like Vietnam. 64 The availability of trained personnel with specialized knowledge and experience in cord blood banking may be limited, particularly in the face of competing demands for healthcare professionals in other areas of the healthcare system. 63 Vietnam is one of the leading nations with a high cancer mortality rate in the world, so preservation of UCB-derived life-saving cells plays a crucial role in a therapeutic application for the future. Advanced technologies that lead to significant breakthroughs in medicine can signal an immediate threat to the expansion of CBBs. For instance, Professor Takanori Takebe and his colleagues recently published an article detailing the process of culturing induced pluripotent stem cells and initiating organogenesis. 65 By overcoming these obstacles, Vietnam can unlock the full potential of CBBs to advance healthcare delivery, research and innovation, and public health outcomes for its population.
Conclusion
To ensure UCB sample storage, compliance with collection, processing, and storage procedures at the CBBs is very important. CBBs are necessary for communicating future health, clinic studies, and regenerative medicine when medical conditions and drug restrictions increase over time. Humanity is seeking a sustainable solution that effectively minimizes the side effects from drugs and treatment chemicals. UCB implies many new, untapped avenues for treating diseases or disorders that have not yet been explored. Besides being a source of autologous and allogeneic UCB grafts, researchers can use it for scientific purposes. CBT is interested in combining with other treatments under the doctor’s prescription so the patient can recover better.
Footnotes
Acknowledgments
The authors acknowledge all participants and the Hi-Tech Center-Vinmec Healthcare System, who helped in conducting this research.
Authors’ Contributions
All authors contributed to and made critical revisions related to the important intellectual content of the review. The first (L.T.T.H.), second (P.N.-T.), and last authors (N.V.-T.) contributed to the collection data and drafted the review. T.V.-P., N.T.-D., L.C.-L., N.K.T., and N.T.M.-T. contributed to the data and drew pictures and wrote reviews. N.V.-T revised the review. All authors contributed to the final version of the review.
Author Disclosure Statement
No conflicting financial interests exist.
Funding Information
There was no funding for this study
