Umbilical Cord Blood Hematopoietic Cells: From Biology to Hematopoietic Transplants and Cellular Therapies.

Umbilical cord blood (UCB) is a rich source of hematopoietic stem and progenitor cells that are biologically superior to their adult counterparts. UCB cells can be stored for several years without compromising their numbers or function. Today, public and private UCB banks have been established in several countries around the world. After 35 years since the first UCB transplant (UCBT), more than 50,000 UCBTs have been performed worldwide. In pediatric patients, UCBT is comparable to or superior to bone marrow transplantation. In adult patients, UCB can be an alternative source of hematopoietic cells when an HLA-matched unrelated adult donor is not available and when a transplant is urgently needed. Delayed engraftment (due to reduced absolute numbers of hematopoietic cells) and higher costs have led many medical institutions not to consider UCB as a first-line cell source for hematopoietic transplants. As a result, the use of UCB as a source of hematopoietic stem and progenitor cells for transplantation has declined over the past decade. Several approaches are being investigated to make UCBTs more efficient, including improving the homing capabilities of primitive UCB cells and increasing the number of hematopoietic cells to be infused. Several of these approaches have already been applied in the clinic with promising results. UCB also contains immune effector cells, including monocytes and various lymphocyte subsets, which, together with stem and progenitor cells, are excellent candidates for the development of cellular therapies for hematological and non-hematological diseases.

Hybrid cord blood banking in a private-public-partnership: Women's perspectives.

BACKGROUND: The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public foreign donor banks and private family-directed donor banks. Recently, our department has introduced a third banking model within a private-public-partnership. This hybrid banking allows for storage of family-directed CB units, while also getting Human leukocyte antigen (HLA)-typed and included in the national stem cell donor registry. So if the need arises, the HLA-compatible CB unit can be released to an unrelated recipient as a foreign donor stem cell graft. OBJECTIVES: The aim of this study was to evaluate women's perspectives on the different CB banking options as well as retrospective satisfaction with their decisions. METHODS: We performed a prospective survey study in postpartum women, using a validated questionnaire. RESULTS: A total of 157 women were included in this survey study; 68% of them decided to have their UCB stored or donated. Among those women, 25% of them opted for hybrid storage, 72% of respondents stored UCB publicly, and 3% decided for private family-directed storage. CONCLUSIONS: Our study shows the potential of hybrid banking as an attractive UCB storage option, as an alternative to family-directed banking rather than a substitute for public donation. Hybrid storage potentially combines advantages of family-directed banking as well as unrelated CB donation expanding the number of registered CB units available for transplantation and giving every pregnant woman the possibility to store UCB.

Hybrid umbilical cord blood banking: literature review.

PURPOSE: Interest gaps between public and private umbilical cord blood banks have led to the introduction of hybrid banking options. Hybrid models combine features of private and public banks as well as interests of parents, children and of patients, in order to find an optimized solution. While several different models of hybrid banks exist, there is a lack of literature about this novel model of cord blood stem cell banking. Therefore, the aim of this literature review is to assess different options of umbilical cord blood banking and whether hybrid banking could be a valuable alternative to the existing public and private cord blood banking models. METHODS: We performed a systematic literature search, using five main databases. Five hybrid models regarding their advantages as well as their challenges are discussed in this review. RESULTS: We found that a wealth of literature exists about public cord blood banking, while private and hybrid banking are understudied. Different modalities of hybrid cord blood banking are being described in several publications, providing the basis to assess different advantages and disadvantages as well as practicability. CONCLUSION: Hybrid banks, especially the sequential model, seem to have potential as an alternative to the existing banking models worldwide. A previously conducted survey among pregnant women showed a preference for hybrid banking, if such an option was available. Nevertheless, opinions among stakeholders differ and more research is needed to evaluate, if hybrid banking provides the expected benefits.

Validity and Reliability of a Questionnaire Developed to Assess the Knowledge of Pregnant Women about Cord Blood Banking

@#Introduction: Cord blood (CB) is rich in hematopoietic stem cells. There has been significant growth in cord blood banks (CBBs) throughout the world. In Malaysia, the CB units cryopreserved in public CBB is below its optimal level. Lack of knowledge about CB banking among mothers in other countries influenced their decision to donate CB, however, there is no local data to support this in Malaysia. Moreover, no validated and reliable tool is available for measuring local women’s knowledge about CB banking. In this study, a questionnaire to assess pregnant women’s knowledge about CB banking was developed and validated. Method: Several steps were taken to develop the knowledge items in the questionnaire which includes comprehensive literature review, content validity by a panel of experts, and face validity by a group of pregnant women. The questionnaire was developed in Malay language and contained 18 items. After modifications, the self-administered questionnaire was distributed to 121 pregnant women to assess its psychometric properties using two-parameter logistic item response theory analysis and internal consistency reliability analysis. Results: The majority of the knowledge items showed acceptable difficulty and discriminatory values. The Cronbach’s alpha and ICC values were 0.831 and 0.887, respectively, indicating good reliability. All 18 knowledge items were retained for the final version of the questionnaire. Conclusion: The newly developed questionnaire demonstrated acceptable psychometric properties and can be used as a reliable tool to assess knowledge about CB banking among pregnant women in the local population.

Drivers of consumers' behavioral intention toward private umbilical cord blood banking: a review.

Immunitary bioeconomy encompasses a significant share of the bioeconomy that is accompanied by a high degree of complexity and various religious and ethical controversies for both customers and the service providers. Compared to blood banking, these complexities are more substantial for the new state-of-the-art technology of umbilical cord blood (UCB) banking, in which the viable therapeutically active substance of cord blood (i.e., cord blood stem cells (CBSCs)) is banked for much less likely future demand. It became even more complicated when we knew that the main three types of cord blood banking industry (i.e., private, public, or hybrid models) are not the same regarding economic, ethical, and even social considerations. The present paper aims to review and discuss the main drivers of behavioral intention among the customers of private UCB banking. We focused on private UCB banking because, although there is a low likelihood of childs' future need for their siblings' CBSCs, there is an unnecessary growing demand for using private UCB banking services. Based on the previously published pieces of research, we discussed five main influential factors (i.e., awareness, reference group, usability, disease history, and price) that can affect the customers' risk perception (and further their behavioral intention) to preserve their child UCB for private applications. Finally, we concluded that private UCB banking must not be considered a commercial activity, and ethically healthcare managers must be more actively involved in facilitating the proper flow of information among the customers.

A Portrait of Cord Blood Units Distributed for Transplantation from Canadian Blood Services' Cord Blood Bank: First Analysis.

BACKGROUND: The Canadian Blood Services Cord Blood Bank (CBS CBB) was created to improve access to stem cell products for transplantation for patients across ethnic groups. An analysis of distributed units is needed to assess the effectiveness of the bank to meet the needs of patients from different ethnic groups. METHODS: A descriptive analysis was performed on all cord blood units distributed from the CBS' CBB as of 30 June 2022. RESULTS: Distribution of the first 60 units based on CBS' CBB inventory has been linear over time. A similar proportion of cord blood unit (CBU) recipients were pediatric or adult. More than half of the cord blood units (56.7%) were distributed to recipients outside of Canada, and CBUs were used to treat a broad range of hematologic and immune disorders. 43.3% of distributed CBUs were of non-Caucasian ethnicity and 18% were from donors self-reporting as multi-ethnic. The mean total nucleated cell counts and total CD34+ cell counts were 1.9 ± 0.1 × 109 cells and 5.3 ± 0.5 × 106 CD34+ cells, respectively. CD34+ cells per kg (recipient weight) varied significantly between pediatric (age 0-4), adolescent (age 5-17) and adult recipients (age 18 and older) (3.1 ± 0.5, 1.4 ± 0.5 and 0.9 ± 0.07 × 105 CD34+ cells/kg, respectively). HLA matching was 6/6 (15%), 5/6 (47%) or 4/6 (38%). CONCLUSIONS: The CBS' CBB has facilitated the utilization of banked units for patients across a broad range of ages, geographic distribution, ethnicity, and diseases. Distributed units were well matched for HLA alleles and contained robust cell counts, reflecting a high-quality inventory with significant utility.

Erratum: Editorial: Umbilical cord blood and tissue in novel therapies and haematopoiesis research.

[This corrects the article DOI: 10.3389/fcell.2022.979306.].

Umbilical Cord Blood Banking: An Update For Childbirth Educators.

To make an informed decision on umbilical cord blood banking or donation during birth, families need evidence-based, quality information on this alternative. Cord blood banking often refers to private banking, while donation generally refers to public banking. Research has shown that expectant parents do not have sufficient understanding of the cord blood banking process, umbilical cord stem cell transplants, uses of these cells, or options. Research also shows that birthing families desire that information to come from a reliable healthcare provider resource, such as a childbirth educator. Therefore, this article will offer information for use by childbirth educators, nurses, or other birth workers to increase awareness and knowledge on the topic of umbilical cord blood banking and donation.

A comprehensive human leukocyte antigen analysis of 36 782 cord blood units stored in the Australian Public Cord Blood Banking Network.

BACKGROUND AND AIMS: The network of public cord blood banks (CBBs) in Australia, known as AusCord, comprises CBBs located in Brisbane, Sydney and Melbourne. A novel comprehensive analysis has been performed to determine whether the cryopreserved, searchable cord blood unit (CBU) inventory of approximately 36 000 units share similar tissue types or haplotypes. METHODS: Human leukocyte antigen (HLA) data was analysed using Microsoft Excel following standardisation of typing data. RESULTS: The analysis has found that the majority of stored, searched and released CBU exhibit a tissue type that is unique within and between the CBBs. Therefore, each collection performed by the CBBs is likely to comprise a tissue type that is not already stored among the total AusCord inventory. HLA alleles (HLA-A*34, HLA-B*56, HLA-DRB1*08:03), which are uncommon in European populations, were associated with Pacific Islander and/or Indigenous Australian populations and confirmed to be more frequent among donors who, when screened, self-identified as these ethnicities. CONCLUSIONS: These data indicate that (i) continued addition of CBU to existing inventories is likely to further increase the HLA diversity and (ii) screening donors for ethnicity or strategically locating collection sites where ethnic minorities reside can successfully result in collection of rare HLA associated with ethnic minority groups for whom finding donors might otherwise be more difficult.

Evidence-based labor management: third stage of labor (part 5).

During the third stage of labor, oxytocin and tranexamic acid, oxytocin and misoprostol, oxytocin and methylergometrine, or carbetocin is recommended for the prevention of postpartum hemorrhage after vaginal delivery. Intravenous oxytocin (10 IU) immediately after delivery of the neonate (after either anterior shoulder or whole-body delivery) and before delivery of the placenta is recommended. If oxytocin and tranexamic acid combination is chosen, intravenous tranexamic acid (1 g) in addition to intravenous oxytocin (10 IU) immediately after delivery of the neonate and before placental delivery is recommended. If oxytocin and misoprostol combination is chosen, sublingual misoprostol (400 µg) in addition to intravenous oxytocin (10 IU) immediately after delivery of the neonate is recommended. If there is no intravenous access or if in low-resource settings, sublingual misoprostol (400 µg) and intramuscular oxytocin (10 IU) are recommended. If oxytocin and methylergometrine combination is chosen, intramuscular methylergometrine (0.2 mg) and intravenous oxytocin (10 IU) immediately after delivery of the neonate are recommended. Single-dose intravenous or intramuscular carbetocin (100 µg) immediately after delivery of the neonate is recommended. Controlled cord traction and delayed cord clamping for approximately 60 seconds is recommended. There is insufficient evidence to support or refute umbilical cord milking, uterine massage, or nipple stimulation for the prevention of postpartum hemorrhage. Repair of first- and second-degree lacerations with continuous synthetic suture technique is recommended. No repair of first-degree lacerations if hemostatic and normal cosmesis can be considered. Repair of third-degree lacerations with end-to-end or overlap continuous synthetic suture technique is recommended. Repair of fourth-degree lacerations with delayed absorbable 4-0 or 3-0 polyglactin or chromic suture in a running fashion is recommended. The use of single-dose second-generation cephalosporin at the time of third- or fourth-degree laceration repairs can be considered. Skin-to-skin contact after delivery is recommended. There is insufficient evidence to support or refute routine cord blood gas sampling after delivery. Public cord blood banking is recommended.

Optimal umbilical cord blood collection, processing and cryopreservation methods for sustained public cord blood banking.

BACKGROUND AIMS: Umbilical cord blood is an established source of stem cells in patients with hematologic malignancies who do not have HLA-compatible matched related or unrelated donors. The success of an umbilical cord blood transplant depends on the dose of total nucleated and CD34+ cells infused. Therefore, collecting, banking and listing high-quality cord blood units with high total nucleated and CD34+ cell dose are essential. METHODS: Here the authors describe their cord blood bank's novel collection technique, which involves both in utero and ex utero collection of a single cord blood unit. The authors also evaluated maternal, neonatal and collection parameters that may impact the cell dose. RESULTS: Maternal gestational age and race, and neonatal weight and sex correlated with the total nucleated cell dose. CONCLUSIONS: The optimized collection of umbilical cord blood is critical for its use as a source of stem cells for transplantation.

Perspectives on establishing a public cord blood inventory in South Africa.

The South African population is highly diverse, both ethnically and genetically. This diversity is particularly true for the African ancestry and various mixed ancestry population groups. These groups are under-represented in national and international bone marrow and peripheral blood donor registries, making it challenging to identify HLA-matched and mismatched unrelated donors when patients from these groups require allogeneic hematopoietic stem and progenitor cell transplantation. In most high-income countries, banked cord blood (CB) units provide an attractive source of hematopoietic progenitor cells for genetically diverse populations. SA does not have a public CB inventory, leaving many patients without access to this important treatment modality. Haploidentical transplantation provides an alternative. In recent years, the use of post-transplant cyclophosphamide has significantly reduced the incidence of graft-versus-host disease after haploidentical transplantation and has improved transplantation outcomes. However, it is difficult to identify suitable haploidentical donors in SA because of family disruption and a high prevalence of HIV. Here the authors provide a brief historical overview of the ethnic and genetic diversity of the country and region. The authors provide a southern African perspective on HLA diversity, consider the allogeneic hematopoietic stem and progenitor cell transplantation landscape and explore the need to establish a public CB bank (CBB) in SA. The health policy and regulatory frameworks that will impact on a CBB in the country SA are also explored. Finally, the authors discuss several matters we believe require attention when considering the establishment of a sustainable public CBB in the South African context.

Predictive analytics and cord blood banking: toward utilization-based unit selection.

BACKGROUND AIMS: Total nucleated cell (TNC) and CD34+ cell doses are considered among the most important parameters when assessing the suitability of a human leukocyte antigen-matched cord blood unit (CBU) for allogeneic hematopoietic stem cell transplantation (HSCT). Cord blood banks therefore frequently select CBUs for cryopreservation based on pre-process TNC content. However, cell loss during processing can lead to a significant quantity of CBUs that do not meet desired post-process quality criteria, and such grafts are less likely to be selected by transplant centers for HSCT. Here the authors present a multi-parameter linear regression (MLR) model capable of identifying CBUs that would process poorly, despite meeting established pre-process TNC and CD34+ quality thresholds. METHODS: Historically processed CBUs were graded from A+ to D depending on post-process cell content, and the utilization rate of each grade category was examined. Eight pre-process predictors of post-process cell content were used to train the MLR model, including red blood cell (RBC) content; CBU volume; age of CBU when received; and TNC constituent cell subsets. The selection efficacy of this model was then compared to that of methods conventionally used to select CBUs for processing, with receiver operating characteristic (ROC) and mean inventory quality analysis forming the basis of assessment. RESULTS: Within the Anthony Nolan Cell Therapy Centre, CBUs graded 'D' accounted for 37% of processing expenditures despite providing only 11% of grafts shipped for HSCT. The MLR model significantly improved pre-process identification of 'D' grade CBUs relative to thresholds based primarily on CD34+ cell content (P < 0.0001) and TNC content (P < 0.0001). At a comparable financial investment, this translated to a banked graft inventory of significantly higher quality than that produced by CD34+ (+8.8% mean increase, P = 0.007) and TNC (+9.9% mean increase, P = 0.010) selection methods. CONCLUSIONS: A predictive modelling approach to pre-process CBU selection is a simple and effective means to increase graft inventory quality and potentially future graft utilization, at no additional financial investment.

Antenatal predictors of stem cell content for successful umbilical cord blood donation.

PURPOSE: The most important HLA-independent factor for the selection of cord blood units (CBU) for hematopoietic stem cell transplantation is the total nucleated cell (TNC) count over 150 × 107 as a surrogate marker for stem cell content. The purpose of this prospective study was to define prenatal clinical predictors for TNC count that would help to identify successful CBU donors before the onset of active labor. METHODS: This was a prospective analysis of 594 CBUs, collected from all eligible term singleton pregnancies at Basel University Hospital between 4/2015 and 9/2016 analyzing several maternal and fetal factors. The impact of these factors on TNC count (< 150 × 107 cells vs. ≥ 150 × 107 cells) of the CBUs was modeled in a multivariate analysis. RESULTS: A total of 114 (19.2%) CBUs had a TNC count of ≥ 150 × 107. In a ROC analysis there was no significant difference between the AUC of all prenatal factors (AUC 0.62) and estimated fetal birth weight by ultrasound alone (AUC 0.62). For women planning a trial of labor a recruitment cut-off at an estimated birth weight of 3300 g would allow 72.6% of all donors with sufficient TNC count to be recruited and 22.8% of all collected CBUs would have a sufficient TNC count for banking. For women planning for elective CS a cut-off of 3400 g would allow 71.4% of all donors with sufficient TNC count to be recruited and 22.7% of all collected CBUs would have sufficient TNC count for banking. CONCLUSION: The estimated fetal birth weight within 2 weeks of delivery by ultrasound as single parameter can be considered at the time of recruitment to estimate the chances of a successful CBU donation.

The Binns Program for Cord Blood Research: A novel model of cord blood banking for academic biomedical research.

Umbilical cord blood is an important graft source in the treatment of many genetic, hematologic, and immunologic disorders by hematopoietic stem cell transplantation. Millions of cord blood units have been collected and stored for clinical use since the inception of cord blood banking in 1989. However, the use of cord blood in biomedical research has been limited by access to viable samples. Here, we present a cost-effective, self-sustaining model for the procurement of fresh umbilical cord blood components for research purposes within hospital-affiliated academic institutions.

Australian maternity healthcare professionals' knowledge, attitudes and practices relevant to cord blood banking, donation and clamp timing: A cross-sectional survey.

PROBLEM: Australian health professionals' knowledge and attitudes towards third stage labour options of cord clamp timing, cord blood banking and donation and their practice of informing parents of these options is unknown. BACKGROUND: Parents have several options for the management of their infant' cord blood during the third stage of labour. Early or deferred cord clamping practices may affect parent choices about physiological transfusion to the neonate and/or cord blood collection for private or public banking or donation. AIM: To identify health professionals' knowledge and attitudes towards third stage labour options of cord clamp timing, cord blood banking and donation and their practice of informing parents of these options. METHODS: A total of 129 Australian maternity healthcare professionals responded to the self-administered survey between December 2017 and June 2018. FINDINGS: Occupational differences were revealed in regard to cord clamp timing, cord blood banking and donation knowledge, attitudes and practices. Midwives were more likely to discuss cord clamp timing with parents and to clamp the cord later than obstetricians. Obstetricians were more knowledgeable of cord blood banking and donation options than midwives. Cord blood banking and donation options were discussed by both groups if parents asked. DISCUSSION: Identification of gaps in knowledge should guide future maternity health professional education that is inclusive of all third stage labour options to ensure that open discussion and informing parents of options is consistent, contemporary and evidence-based. CONCLUSION: To make informed decisions, parents need evidence-based information on all third stage labour options.

Changes in Knowledge about Umbilical Cord Blood Banking and Genetic Tests among Pregnant Women from Polish Urban and Rural Areas between 2010-2012 and 2017.

The aim of this study was to evaluate knowledge of umbilical cord blood (UBC) banking and prenatal genetic diagnosis among pregnant women from rural and urban areas, and how this knowledge changed within a five-year period. A survey by questionnaire was conducted between 2010 and 2012, and in 2017 in public hospitals; the study population comprised 6128 women, with 2797 patients from the years 2010-2012 and 3331 from the year 2017. 41% of the studied population declared that they were living in rural areas. In the 2010-2012 period, fewer women from rural areas knew about UBC banking. In 2017 that same relative difference in knowledge persisted, but the percentage of women who now knew about this procedure rose significantly in both studied groups. Prenatal diagnosis was more familiar for urban inhabitants both in 2010 and 2017 but as with the UBC data, a trend of growing awareness was also seen in pregnant women from rural areas. Knowledge of new techniques such as UBC banking and genetic tests has grown among pregnant women during the time frame of our study, but there is still a need to emphasize the benefits of these two possibilities to pregnant women, especially among rural inhabitants.

Maternity health professionals' perspectives of cord clamp timing, cord blood banking and cord blood donation: a qualitative study.

BACKGROUND: Parents today have several options for the management of their infant's cord blood during the third stage of labour. Parents can choose to have their infant's cord clamped early or to have deferred cord clamping. If the cord is clamped early, cord blood can be collected for private cord blood banking or public cord blood donation for use later if needed. If cord clamping is deferred, the placental blood physiologically transfuses to the neonate and there are physiological advantages to this. These benefits include a smoother cardiovascular transition and increased haemoglobin levels while not interfering with the practice of collecting cord blood for gases if needed. The aim of this study is to explore Australian maternity health professionals' perspectives towards cord clamp timing, cord blood banking and cord blood donation. METHODS: Fourteen maternity health professionals (midwives and obstetricians) from both private and public practice settings in Australia participated in semi-structured interviews either in person or by telephone. Interviews were transcribed and data analysed using thematic analysis. RESULTS: Overall there was strong support for deferred cord clamping, and this was seen as important and routinely discussed with parents as part of antenatal care. However, support did not extend to the options of cord blood banking and donation and to routinely informing parents of these options even when these were available at their birthing location. CONCLUSION: Formalised education for maternity health professionals is needed about the benefits and implications of cord blood banking and cord blood donation so that they have the confidence to openly discuss all options of cord clamp timing, cord blood banking and cord blood donation to facilitate informed decision-making by parents.