Biochemical and Biophysical Research Communications
Hematopoietic capacity of preterm cord blood hematopoietic stem/progenitor cells
Introduction
Since the first successful cord blood transplantation in a child with Fanconi anemia in 1988 [1], several hundred patients with hematological malignancies or genetic diseases affecting the hematopoietic system have been treated through cord blood (CB) transplantation from both related and unrelated donors [2], [3]. In addition, stem cells in CB are an attractive target for somatic gene therapy to treat inborn defects of the lymphoid and hematopoietic systems [4], [5]. In clinical application, infusion of higher numbers of nucleated and CD34+ cells has proven to be a major predictor of faster engraftment and prolonged survival [3], [6]. For that reason, CB banks established a policy of selecting units with high numbers of total nucleated and CD34+ cells [7].
Previous studies have shown that the frequency of primitive hematopoietic stem/progenitor cells (HSCs/HPCs) and their proliferative capacity are higher in CB from fetuses at a very low gestational age and in preterm CB (PCB) than in CB at term (TCB) [8], [9], [10], [11], [12], [13], [14]. This property suggests that PCB may be a useful source for stem cell transplantation and gene therapy. Although the hematopoietic properties of CB from full-term newborns have been well characterized, little is known about the hematopoietic capacity of HSCs from PCB, particularly their homing and repopulating capabilities. We previously established a xenotransplantation system for evaluating human HSC activity using NOD/Shi-scid (NOD/SCID) mice, which exhibit macrophage dysfunction and lack mature lymphocytes and circulating complements [15]. The aim of the present study was to investigate the immunophenotypic changes induced by PCBs and TCBs and assess their capacities for homing and bone marrow (BM) reconstitution.
Section snippets
Methods
For the purpose of this analysis, infants were subdivided into two groups using 37 weeks as the cut-off gestational age. These groups were designated PCB and TCB.
Collection of umbilical cord blood. Informed consent for CB collection was obtained from 57 healthy women with uncomplicated pregnancies, and all experiments were approved by the Ethical Committee of the Japanese Red Cross Katsushika Maternity Hospital in Tokyo, Japan. CB was collected into sterile heparinized tubes outside the delivery
Volume of cord blood samples, gestational age
The mean volume of the collected CB samples was 22.4 ± 12.7 ml for the PCB group (n = 26) and 26.9 ± 18.5 ml for the TCB group (n = 31) (Table1).
MNC content and phenotypic characterization of CD34+ cells in PCB and TCB
The characteristics of PCB and TCB are summarized in Table 1. The numbers of MNCs/ml of CB were significantly higher in the TCB group (5.3 ± 5.3 × 106/ml) than the PCB group (2.2 ± 2.3 × 106/ml, p < 0.01). Among MNCs, the proportion of CD34+ cells was significantly higher in PCB than in TCB (2.4 ± 1.8%; range 0.6–7.1% vs. 0.9 ± 0.4%; range 0.2–1.6%, p < 0.01). However, the
Discussion
In the present study, we have shown that CD34+CD38− cells, a subpopulation of CD34+ cells, accounted for a significantly higher proportion of cells in PCB than in TCB. On the other hand, our experiments with NOD/SCID mice showed that HSCs from TCB have greater homing ability than HSCs from PCB, and that the lower engraftment rate following transplantation of HSCs from PCB is related to the weaker expression of homing-related molecules.
In HSC transplants, the number of CD34+ cells in the donor
Acknowledgments
This study was supported in part by grant from the Ministry of Health, Labour, and Welfare of Japan.
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Cited by (6)
Stem Cells: Potential Therapy for Neonatal Injury?
2015, Clinics in PerinatologyCitation Excerpt :The proportions of CD34+ cells in preterm CB are generally higher than in full-term CB, although the absolute numbers of CD34+ cells reported have been variable. Although preterm CB CD34+ cells exhibit higher colony-forming ability than full-term CB CD34+ cells,52 preterm CD34+ cells may have lower repopulating ability.51 The ability of transplanted CD34+ cells to repopulate the BM in patients with SCID has been shown to correlate with the expression level of CXCR4, a surface receptor involved in cellular migration and homing to the BM.42
Generation of hematopoietic humanized mice in the newborn BALB/c-Rag2<sup>null</sup>Il2rγ<sup>null</sup> mouse model: A multivariable optimization approach
2011, Clinical ImmunologyCitation Excerpt :Understanding of human HSC biology has improved through research aimed at increasing the efficiency of bone marrow, umbilical cord blood and mobilized peripheral blood transplantation in the clinic. For instance, although the CD34 antigen is commonly accepted as a primitive hematopoietic stem cell marker, subsets within the CD34+ cells exist and display varying degrees of engraftment potential [11–16]. In addition, effort has focused on expanding HSCs in culture, testing the effect of cytokines and media in this context [17,18].
Maternal and neonatal variables affecting CD34+ cell count in the umbilical cord blood
2022, Journal of Applied Hematology