The impact of antenatal and perinatal variables on cord blood haemopoietic stem/progenitor cell yield available for transplantation

Abstract

Summary.We investigated the impact of maternal and fetal variables on cord blood (CB) haemopoietic stem/progenitor cell content. These included maternal age, ethnic origin, parity, ABO and Rhesus D blood group, antenatal haemoglobin, alcohol and cigarette consumption at time of registration, mode of delivery, duration of the first and second stages of labour, gestational age, birth weight, cord pH and cord erythrocyte mean cell volume (MCV). Cord volumes and total nucleated cellularities (TNC) were recorded, the colony assay for granulocyte-macrophage colony-forming-cells (CFU-GM) was used to quantify the progenitor cells and the potential of CFU-GM to produce secondary colonies on replating was used as a measure of progenitor cell quality. We found: (1) significantly greater ( P ¼ 0·04) volumes were collected from babies who weighed у 2·5 kg versus babies with a birth weight < 2·5 kg; (2) significantly greater numbers of mononuclear cells (MNC) from mothers who drank 0-3 units versus those who drank у 4 units of alcohol weekly ( P ¼ 0·03), and in babies with a cord pH р 7·1 v > 7·1 ( P ¼ 0·02); (3) Significantly greater numbers of cord CFU-GM in mothers who drank 0-3 v у 4 units weekly ( P ¼ 0·004) and smokers of у 10 v 0-9 cigarettes daily ( P ¼ 0·02) and in spontaneous vaginal deliveries than assisted vaginal and caesarean deliveries ( P ¼ 0·04), and (4) the potential of CFU-GM to produce secondary colonies was significantly greater in CB derived from Caucasians than from non-Caucasians ( P ¼ 0·02); in assisted vaginal delivery v spontaneous vaginal ( P ¼ 0·02) and in deliveries with prolonged first stage of labour v short first stage of labour ( P ¼ 0·04). We conclude that antenatal and perinatal variables may influence the CB stem/ progenitor cell yield available for transplantation.Keywords: maternal factors, fetal factors, progenitor assays, AUC.Human cord blood (CB) is an alternative source of haemopoietic stem cells for clinical transplantation. Over 500 related and unrelated CB transplants have been undertaken, mostly in children. The availability of CB may shorten the period needed to search for an unrelated donor in the case of recipients who have no sibling donor. Rubinstein et al (1993) found that unrelated cord blood was available at a median of 69 d versus > 2·5 months for bone marrow. More recently, during a search for unrelated CB for 85 high-risk leukaemic patients (Gluckman, personal communication), potential donations were identified for 65/ 85 patients (76%) at a median of 4 d (range 0-586); of these 59 donations fully eligible for transplantation were identified for 34 patients (40%) after a median of 47 d (1-449).The contribution of CB to adult transplantation remains limited due to the restricted number of stem/ progenitor cells available in CB donations (Wagner et al,

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk

“…This association is strongest with CD34 þ CD38 À cells, a relatively primitive haematopoietic stem cell population. These data are in line with previous studies, which showed a positive relationship between cord blood CD34 þ or CFU-GM levels and birth weight (Shlebak et al, 1998;Ballen et al, 2001;Aroviita et al, 2004). However, in our study, newborns in the lowest birth weight category (o3000 g) can have higher levels of stem/progenitor cell measurements than those with 3000 -3499 g birth weight resulting in a J-or U-shaped relation between stem cell levels and birth weight.…”

Umbilical cord blood for allogeneic transplantation in children and adults

“…[12][13][14][15][16][17][18][19] UCB collection is performed during the final phase of labor or, more commonly, after delivery of Correspondence: Dr MJ Laughlin, Case Western Reserve University, University Hospitals Ireland Comprehensive Cancer Center, 11100 Euclid Avenue, Wearn 433, Cleveland, Ohio 44106-5065, USA Table 1 Advantages of UCB as hematopoietic stem cells for allogeneic transplantation 1 Placental or umbilical cord blood is an abundantly available source of stem cells which can be harvested at no risk to the mother or infant. 2 Ethnic balance in a cord blood repository can be maintained automatically in heterogeneous populations or can be controlled via collection from birthing centers representing targeted minority populations.…”

“…[12][13][14][15][16][17][18][19] UCB collection is performed during the final phase of labor or, more commonly, after delivery of…”

Cord blood collection and banking from a population with highly diverse geographic origins increase HLA diversity in the registry and do not lower the proportion of validated cord blood units: experience of the Marseille cord blood bank

“…Indeed, the Bone Marrow Donors Worldwide collaboration of registries presents a lack of genetic diversity with an over-representation of donors from Northwestern European descent. 4,6,7,[10][11][12][13][14] Thus, patients with non-European ancestry have lower odds of obtaining a graft with high HLA compatibility and/or high TNCC. [13][14][15][16] These studies highlight the importance of developing CB banking in partnership with birth clinics that care for pregnant women originating from populations that are underrepresented in existing CBBs and registries.…”

“…Many studies have shown that volume and TNC and progenitor counts are correlated. [6][7][8][9][10] Besides CBU cell content, a central issue of CB banking raised by many authors is HLA diversity. Indeed, the Bone Marrow Donors Worldwide collaboration of registries presents a lack of genetic diversity with an over-representation of donors from Northwestern European descent.…”