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Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants
Zhou, L., McDonald, C. A., Yawno, T., Penny, T., Miller, S. L., Jenkin, G., Malhotra, A.
Cytotherapy. 2023
Abstract
BACKGROUND AIMS Umbilical cord blood (UCB)-derived cells show strong promise as a treatment for neonatal brain injury in pre-clinical models and early-phase clinical trials. Feasibility of UCB collection and autologous administration is reported for term infants, but data are limited for preterm infants. Here the authors assessed the feasibility of UCB-derived cell collection for autologous use in extremely preterm infants born at less than 28 weeks, a population with a high incidence of brain injury and subsequent neurodisability. METHODS In a prospective study at a tertiary hospital in Melbourne, Australia, UCB was collected from infants born at less than 28 weeks and processed to obtain total nucleated cells (TNCs), CD34+ cells, mononuclear cells and cell viability via fluorescence-activated cell sorting prior to cryopreservation. Feasibility was pre-defined as volume adequate for cryopreservation (>9 mL UCB collected) and >25 × 10(6) TNCs/kg retrieved. RESULTS Thirty-eight infants (21 male, 17 female) were included in the study. Twenty-four (63.1%) were delivered via cesarean section, 30 (78.9%) received delayed cord clamping before collection and 11 (28.9%) were a multiple birth. Median (interquartile range [IQR]) gestational age was 26.0 weeks (24.5-27.5) and mean (standard deviation) birth weight was 761.5 g (221.5). Median (IQR) UCB volume collected was 19.1 mL/kg (10.5-23.5), median (IQR) TNC count was 105.2 × 10(6)/kg (57.4-174.4), median (IQR) CD34+ cell count was 1.5 × 10(6)/kg (0.6-2.1) and median (IQR) cell viability pre-cryopreservation was 95% (92.1-96.0). Feasibility of collection volume and cell count suitable for cell cryopreservation was achieved in 27 (71%) and 28 (73.6%) infants, respectively. CONCLUSIONS UCB-derived cell collection adequate for cryopreservation and subsequent autologous reinfusion was achieved in 70% of extremely preterm infants. Extremely preterm UCB demonstrated a higher CD34+:TNC ratio compared with published full-term values. Recruitment to demonstrate safety of UCB cell administration in extremely premature infants is ongoing in the CORD-SAFE study (trial registration no. ACTRN12619001637134).
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Effect of cord blood double collection method on cord blood hematopoietic stem cell transplantation-related indices and blood gas analysis
Shi, C., Rao, W., Huang, W., Ma, T., Wei, W.
Medicine. 2023;102(47):e36227
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Abstract
BACKGROUND Umbilical cord blood has been widely used in clinical transplantation. Blood gas analysis of umbilical cord blood is routinely used to evaluate neonatal asphyxia. This study aimed to evaluate an improved umbilical cord blood collection method that does not affect the results of umbilical cord blood gas analysis and hematopoietic stem cell transplantation-related indices. METHODS Three hundred pregnant women were recruited between December 2019 and August 2022. In total, 270 umbilical cord blood samples were included and randomly divided into 3 groups. Group A was defined as the group in which both umbilical cord blood samples for hematopoietic stem cell transplantation and blood gas analysis were collected. Group B was defined as the group from which umbilical cord blood was collected for hematopoietic stem cell transplantation. Group C was defined as that wherein umbilical cord blood was collected only for blood gas analysis. Hematopoietic stem cell transplantation-related indices were detected in groups A and B, and blood gas analysis was performed in groups A and C. RESULTS Hematopoietic stem cell transplantation-related indices were not significantly different between groups A and B. The pH, base excess, and lactic acid values were not significantly different between groups A and C. CONCLUSION The cord blood double collection method would not affect the results of umbilical cord blood gas analysis and hematopoietic stem cell transplantation-related indices. It is suitable for cord blood collection when preparing for hematopoietic stem cell transplantation and blood gas analysis.
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Predictors of cord blood unit cell content in a volume unrestricted large series collections: a chance for a fast and cheap multiparameter selection model
Fumarola, S., Lucarini, A., Lucchetti, G., Piroli, L., Pierelli, L.
Stem cell research & therapy. 2022;13(1):246
Abstract
BACKGROUND Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. METHODS Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. RESULTS Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie's gender and birth weight have a positive correlation with CB TNC content. The babie's birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie's, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 10(8) (group A) have a significant higher CD34+ content than group B (female babies, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 10(6), while no CBUs with high concentration of CD34+ were detect in group B. CONCLUSION This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries.
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Prenatal selection of cord blood donors according to the estimated fetal weight percentile and new approaches; results of a prospective cohort study
Xinxin, L., Crovetto, F., González, A., Cuadras, D., Sanchez, M., Azqueta, C., Farssac, E., Torrabadella, M., Querol, S., Gomez-Roig, M. D.
Transfusion. 2021;61(4):1215-1221
Abstract
BACKGROUND Umbilical cord blood (UCB) donation is becoming inefficient and we recently proposed the estimated fetal weight percentile (EFWp) ≥60th as a predictor for a prenatal selection of donors. The aim of this study is to prospectively validate this and to identify new potential prenatal predictive parameters. STUDY DESIGN AND METHODS Prospective cohort study of low-risk pregnancies undergoing third trimester ultrasound, whose UCB was collected at delivery (2016-2018) and compared with a historical cohort (2013-2016, N = 869). Several ultrasound parameters (EFWp, amniotic fluid, Doppler evaluation, placental thickness) were assessed ultrasound and perinatal data were collected. The association with standard of high quality of UCB was assessed by logistic regression analysis. RESULTS Among 297 cases, 161 (54%) were selected according to the EFWp ≥60th for UCB units' collection. Cellular criteria for banking was achieved in 27 cases (16.8%), with an average increase of 1.7 times compared to the historical cohort (9.8%, P = .009). Selecting donors according to the 60th EFWp resulted in a higher probability of collecting clinical suitable UCB (P = .025). Among prenatal and perinatal parameters, EFWp, amniotic fluid, umbilical vein (UV) velocity, newborn weight and percentile and placental weight were significantly associated with a higher cellular content. At logistic regression analysis, significant contributors of UCB collection, were EFWp at 37-38 weeks ultrasound (OR 1.04; 95% CI: 1-1.08; P = .042) and UV velocity (OR 1.14; 95% CI: 1-1.29; P = .037). CONCLUSION The evaluation of the EFWp equal or above 60 and the increased UV velocity can result in higher efficiency of public UCB donation programs.
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[Harvest of Stem Cells from Umbilical Cord Blood: Relevance of Perinatal Factors for the Quality of Umbilical Cord Transplant Units]
Farina-Eckhardt, P., Granado, C., Mueller-Borer, D., Schötzau, A., Tsakiris, D. A., Hösli, I., Manegold-Brauer, G.
Zeitschrift fur Geburtshilfe und Neonatologie. 2021
Abstract
INTRODUCTION Umbilical cord blood (UCB) contains hematopoietic stem cells with therapeutic potential and unique cellular properties. Due to the limited number of stem cells in the UCB (surrogate marker total nucleated cells, TNC), only one in five donations is suitable for transplantation. The aim of this study was to investigate whether predictive factors exist for a TNC count above the 99th percentile. MATERIAL AND METHODS Retrospective data analysis of the 100 largest donations from 2,299 registered UCB units. Differences between maternal, fetal, and obstetric factors were analyzed and compared with a standardized cohort of 731 registered UCB units. RESULTS maternal age and BMI in the Top100 cohort were higher compared with the comparative cohort (32 vs. 31 years, p=0.007; 30?kg/m2 vs. 29?kg/m2, p=0.024). There were significantly more P1 (76.0 vs. 62.8%, p=0.013) and women with gestational diabetes (5.00 vs. 1.65%, p=0.044). The gestational week, birth weight, the proportion of vaginal-operative deliveries and secondary caesarean sections were higher in the Top100 cohort (40+4 vs. 40+1 wks, p=0.002), (3700 vs. 3450?g, p<0.001), (53.0 vs. 22.7%, p<0.001) (10 vs. 6.2%, p=0.014). CONCLUSION For a successful transplant, the amount of TNC in the UCB unit is crucial. Vaginal-operative deliveries, secondary caesarean sections, and a birth weight above 3700?g are favorable with regard to stem cell content. In cases with a complicated course of delivery, collection should not be neglected once the mother and child are safely cared for.
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Feasibility of Umbilical Cord Blood Collection in Neonates at Risk of Brain Damage-A Step Toward Autologous Cell Therapy for a High-risk Population
Segler, A., Braun, T., Fischer, H. S., Dukatz, R., Weiss, C. R., Schwickert, A., Jäger, C., Bührer, C., Henrich, W.
Cell transplantation. 2021;30:963689721992065
Abstract
Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) =30 + 0 weeks and/or birthweight <1,500 g, intrauterine growth restriction (IUGR), or monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of collection, quantity and quality of obtained UCB [total nucleated cell count (TNC), volume, sterility, and cell viability], and neonatal outcome were assessed. UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA =30 + 0 weeks n = 54; IUGR n = 71; TTTS n = 6). Twenty-six cases were missed. The amount of missed cases per month declined over the time. Volume of collected UCB ranged widely (median: 24.5 ml, range: 5.0-102 ml) and contained a median of 0.77 × 10(8) TNC (range: 0.01-13.0 × 10(8)). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB.
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Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience
Adams, Z., Morris, G., Campbell, T., Mostert, K., Dibdin, N., Fearon, M., Elmoazzen, H., Mercer, D., Young, K., Allan, D.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018;24(4):861-865
Abstract
Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended.
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A new strategy for umbilical cord blood collection developed at the first Colombian public cord blood bank increases total nucleated cell content
Vanegas, D., Trivino, L., Galindo, C., Franco, L., Salguero, G., Camacho, B., Perdomo-Arciniegas, A. M.
Transfusion. 2017;57(9):2225-2233
Abstract
BACKGROUND The total nucleated cell dosage of umbilical cord blood (UCB) is an important factor in determining successful allogeneic hematopoietic stem cell transplantation after a minimum human leukocyte antigen donor-recipient match. The northern South American population is in need of a new-generation cord blood bank that cryopreserves only units with high total nucleated cell content, thereby increasing the likelihood of use. Colombia set up a public cord blood bank in 2014; and, as a result of its research for improving high total nucleated cell content, a new strategy for UCB collection was developed. STUDY DESIGN AND METHODS Data from 2933 collected and 759 cryopreserved cord blood units between 2014 and 2015 were analyzed. The correlation of donor and collection variables with cellularity was evaluated. Moreover, blood volume, cell content, CD34+ count, clonogenic capacity, and microbial contamination were assessed comparing the new method, which combines in utero and ex utero techniques, with the conventional strategies. RESULTS Multivariate analysis confirmed a correlation between neonatal birth weight and cell content. The new collection method increased total nucleated cell content in approximately 26% and did not alter pre-cryopreservation and post-thaw cell recovery, viability, or clonogenic ability. Furthermore, it showed a remarkably low microbial contamination rate (1.2%). CONCLUSION The strategy for UCB collection developed at the first Colombian public cord blood bank increases total nucleated cell content and does not affect unit quality. The existence of this bank is a remarkable breakthrough for Latin-American patients in need of this kind of transplantation.
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Time related variations in stem cell harvesting of umbilical cord blood
Mazzoccoli, G., Miscio, G., Fontana, A., Copetti, M., Francavilla, M., Bosi, A., Perfetto, F., Valoriani, A., De Cata, A., Santodirocco, M., et al
Scientific Reports. 2016;6:21404
Abstract
Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units.
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A novel, bedside technique to rapidly identify umbilical cord blood units with high total nucleated cell numbers
Wagner, A. M., Krenger, W., Stettler, S., Beutler, E., Herbst, J., Surbek, D. V., Baerlocher, G. M.
Transfusion. 2016;56(6):1406-12
Abstract
BACKGROUND With increasing demand for umbilical cord blood units (CBUs) with total nucleated cell (TNC) counts of more than 150 x 10(7) , preshipping assessment is mandatory. Umbilical cord blood processing requires aseptic techniques and laboratories with specific air quality and cleanliness. Our aim was to establish a fast and efficient method for determining TNC counts at the obstetric ward without exposing the CBU to the environment. STUDY DESIGN AND METHODS Data from a total of 151 cord blood donations at a single procurement site were included in this prospective study. We measured TNC counts in cord blood aliquots taken from the umbilical cord (TNCCord ), from placenta (TNCPlac ), and from a tubing segment of the sterile collection system (TNCTS ). TNC counts were compared to reference TNC counts in the CBU which were ascertained at the cord blood bank (TNCCBU ). RESULTS TNCTS counts (173+/-33 x 10(7) cells; calculated for 1 unit) correlated fully with the TNCCBU reference counts (166+/-33 x 10(7) cells, Pearson's r=0.97, p<0.0001). In contrast, TNCCord and TNCPlac counts were more disparate from the reference (r=0.92 and r=0.87, respectively). CONCLUSIONS A novel method of measuring TNC counts in tubing segments from the sterile cord blood collection system allows rapid and correct identification of CBUs with high cell numbers at the obstetric ward without exposing cells to the environment. This approach may contribute to cost efficacy as only CBUs with satisfactory TNC counts need to be shipped to the cord blood bank. Copyright © 2016 AABB.