A Modified Cord Blood Collection Method Achieves Sufficient Cell Levels for Transplantation in Most Adult Patients

Abstract

Umbilical cord blood transplantation (UCBT) has been used increasingly in both pediatric and adult patients. The total nucleated cell (NC) dose infused is the most critical factor in determining speed of engraftment and survival. Using standard collection techniques, the mean NC content of UCB units is about 10 × 10 8, and only 25% of these units reach the target cell dose of 2 × 10 7 /kg in UCBT patients weighing 50-70 kg. We have designed a modified placental/umbilical two-step collection method in which a standard blood fraction obtained by umbilical venipuncture is combined with a second fraction harvested after placental perfusion with 50 ml heparinized 0.9% saline. This second fraction contributed 32% volume and 15% NCs to the whole UCB unit (123.7 ± 50.1 ml and 1.26 ± 0.52 × 10 9 NC). The proportion of progenitor cells in both fractions was not significantly different, indicating that the hematopoietic potential of these larger units is 20% (range, 2%-100%) higher than UCB units collected by standard methods. In addition, the bacterial contamination rate associated with this novel collection method (2.78%) compares favorably. Since 1998 we have further enriched our units by processing only UCB units over 0.8 × 10 9 NCs, resulting in a 36% cell increment (1.46 ± 0.52 × 10 9 NCs). Thus, 84% and 54% of the Madrid UCB Bank inventory would fulfill the target cell dose of 2 × 10 7 /kg in patients weighing 50 and 65 kg, respectively. This significant UCB banking improvement gives larger pediatric and adult patients a greater chance of finding adequate grafts in order to achieve better clinical outcomes after UCBT. Stem Cells 2005;23:324-334

Maternal and Neonatal Factors Associated with the High Yield of Mononuclear Low-Density/CD34+ Cells from Placental/Umbilical Cord Blood

“…These results are consistent with most of the previous reports (Donaldson et al 1999;Yamada et al 2000;Li et al 2001;George et al 2006;Mancinelli et al 2006), including that meconium in the amniotic fluid correlates with better cell counts (Askari et al 2005). Therefore the total LD cells per CB unit analyzed in the present study can be assumed as a substitute variable instead of the total nucleated cells in some previous studies (Lasky et al 2002;Mohyeddin Bonab et al 2004;Solves et al 2005), and can be also confirmed by other previous studies (Pafumi et al 2001;Bornstein et al 2005). In addition, the univariate analyses also show the significantly positive correlations between neonatal birth weight, placental weight, net weight of CB, and gestational age (Fig.…”

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

“…The authors suggested that the multi-step RWV bioreactor could expand a single cord blood to reach 1.2 9 10 9 MNC, enough to transplant an 80 kg patient (with the minimal amount of 1.5 9 10 7 CMN/kg). However, the cell dose is below the standards defined in the current guidelines for transplantation (Bornstein et al 2005). The National Aeronautics and Space Administration (NASA) developed two RWV bioreactors for tissue mass culture (Martin and Vermette 2005).…”

“…Umbilical cord blood (UCB) is other major source of HSC, which has been successfully used for transplantation since 1989 (Gluckman et al 1989). The possibility of creating UCB banks is a reality (Bornstein et al 2005); therefore UCB is increasingly gaining attention as a reliable source of HSC for transplantation, and it is currently an accepted therapy for several diseases. Bone marrow and peripheral blood stem cells autologous transplantation reduces the risk of immunological rejection and are preferred as therapeutic approaches.…”

“…The main drawback in UCB transplantation is the low quantity of HSC, since the content per UCB unit ranges between 0.4 and 1.0 9 10 9 total mononuclear cells (MNC), whereas the dose currently recommended ranges from 2.0 9 10 7 to 2.5 9 10 7 MNC/kg. A dose lower than 1.5 9 10 7 MNC/kg showed poor results (Bornstein et al 2005), thus restricting UCB transplantation to pediatric patients in most of the cases. Since the biology of HSC and their microenvironment are not totally understood (Hofmeister et al 2007), it has not been easy to overcome this issue.…”

SDF-1/CXCR4 blockade to mobilize hematopoietic progenitor cells from the placenta

“…1 Therefore, several groups are working on an optimized collection procedure in order to increase the number of transplantable progenitors. Bornstein et al 2 have demonstrated recently that a modified in utero/ex utero two-step collection procedure can lead to a significant increase in the number of harvested progenitor cells.…”