Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

Almici, Camillo; Carlo‐Stella, Carmelo; Wagner, JE; Mangoni, L; Garau, D.; Rizzoli, Vittorio

doi:10.1038/sj.leu.2400871

Cited by 27 publications

(15 citation statements)

References 38 publications

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“…Later on, spleen and, predominantly, fetal liver are organs of hematopoiesis before the bone marrow starts to play a leading role (20). Umbilical cord blood contains many hematopoietic progenitor cells (21)(22)(23). In agreement with the higher ex vivo proliferative potential of purified progenitor cells from cord blood compared with adult bone marrow (24), significantly longer telomeres have been observed in umbilical cord blood (14).…”

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confidence: 56%

Telomeres in Neonates: New Insights in Fetal Hematopoiesis

et al. 2001

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Progressive telomere shortening occurs in somatic cells, and with increasing donor age a significant decline in telomere length has been shown in various postnatal tissues. In contrast, little is known about changes in telomere length during human fetal development. Therefore, we measured telomere length in the leukocyte fraction of umbilical cord blood samples from 15 preterm (Ͻ37 wk of gestation) and 11 full-term (Ͼ37 wk of gestation) neonates using the telomere restriction fragment assay. Whereas no differences in mean (Ϯ SD) telomere restriction fragment between the groups of preterm neonates (8512 Ϯ 523 bp) and full-term newborns (8323 Ϯ 503 bp) could be found, significantly longer telomeres (p ϭ 0.002) were found in very low birth weight preterm neonates when compared with low birth weight preterm neonates. In addition, a rapid and significant decline in mean telomere restriction fragment was observed between 27 and 32 wk of gestation (p ϭ 0.02, r ϭ 0.79) followed by a period of no significant loss of telomere repeats between 33 and 42 wk of gestation. These results are consistent with the known almost maximal proliferation rate of hematopoietic progenitor cells before 32 wk of gestation. The initial decrease in telomere restriction fragment could be caused by ontogenyrelated functional alterations of hematopoietic cells or differences in stem cell turnover or the rate of telomere loss per cell division. Telomeres play a major role in chromosome structure and function by protecting their degradation and apparently contributing to the attachment of chromosome ends to the nuclear envelope. Telomeres lose a portion of their noncoding repetitive DNA sequences with each cell division, and the ribonucleoprotein enzyme telomerase can compensate for this by synthesis of telomere repeats onto chromosomes (1-3). Despite the observation that some immortalized cell lines manifest stable telomeres without evidence of telomerase activity (4), telomerase-dependent telomere elongation seems to be the most important mechanism for maintaining telomere length in vitro and in vivo.In man telomerase is expressed during embryogenesis. Ulaner and Giudice (5) examined telomerase activity in various fetal tissues from 8 to 21 wk of gestation. They found that all tissues expressed telomerase at the earliest ages analyzed, followed by tissue-specific suppression during embryogenic development. After birth this enzyme is repressed in most somatic tissues (6), and high activity persists only in germline cells.Whereas in most postnatal somatic tissues telomerase is not expressed, low levels of this enzyme are detected in hematopoietic progenitor cells, activated lymphocytes (7), intestinal crypt cells (8), the basal layer of the skin (9), and during the proliferative phase in the premenopausal endometrium (10, 11). It is assumed that the low telomerase activity compensates the increased loss of telomere repeats associated with the high rate of cell turnover in these tissues. However, in contrast to germline and tumor cells, these low l...

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confidence: 56%

Telomeres in Neonates: New Insights in Fetal Hematopoiesis

et al. 2001

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“…1,2 However, several phenotypic and functional differences between hematopoietic stem cells from these three tissues have been described during the last few years. [3][4][5][6] The CD34…”

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Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Bruyn

Delforge

Lagneaux

et al. 2000

Bone Marrow Transplant

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“…Timeus et al (9) observed that the number of CD34 + CD38 -cells was significantly higher in cord blood than in bone marrow (16 ± 8.8 and 4.7 ± 3% of total CD34 + cells, respectively). However, the number of CD38 -cells among HUCB CD34 + cells was reported as 11% (18), or 34.9 ± 3.4% (20).…”

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confidence: 99%

Immunophenotype of hematopoietic stem cells from placental/umbilical cord blood after culture

Pranke

Hendrikx

Debnath

et al. 2005

Braz J Med Biol Res

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Identification and enumeration of human hematopoietic stem cells remain problematic, since in vitro and in vivo stem cell assays have different outcomes. We determined if the altered expression of adhesion molecules during stem cell expansion could be a reason for the discrepancy. CD34+CD38- and CD34+CD38+ cells from umbilical cord blood were analyzed before and after culture with thrombopoietin (TPO), FLT-3 ligand (FL) and kit ligand (KL; or stem cell factor) in different combinations: TPO + FL + KL, TPO + FL and TPO, at concentrations of 50 ng/mL each. Cells were immunophenotyped by four-color fluorescence using antibodies against CD11c, CD31, CD49e, CD61, CD62L, CD117, and HLA-DR. Low-density cord blood contained 1.4 ± 0.9% CD34+ cells, 2.6 ± 2.1% of which were CD38-negative. CD34+ cells were isolated using immuno-magnetic beads and cultured for up to 7 days. The TPO + FL + KL combination presented the best condition for maintenance of stem cells. The total cell number increased 4.3 ± 1.8-fold, but the number of viable CD34+ cells decreased by 46 ± 25%. On the other hand, the fraction of CD34+CD38- cells became 52.0 ± 29% of all CD34+ cells. The absolute number of CD34+CD38- cells was expanded on average 15 ± 12-fold when CD34+ cells were cultured with TPO + FL + KL for 7 days. The expression of CD62L, HLA-DR and CD117 was modulated after culture, particularly with TPO + FL + KL, explaining differences between the adhesion and engraftment of primary and cultured candidate stem cells. We conclude that culture of CD34+ cells with TPO + FL + KL results in a significant increase in the number of candidate stem cells with the CD34+CD38- phenotype

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Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood

Cited by 27 publications

References 38 publications

Telomeres in Neonates: New Insights in Fetal Hematopoiesis

Telomeres in Neonates: New Insights in Fetal Hematopoiesis

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Immunophenotype of hematopoietic stem cells from placental/umbilical cord blood after culture

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