Article

Telomere length and proliferation potential of hematopoietic stem cells

Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Journal of Cell Science (Impact Factor: 5.33). 02/1995; 108 ( Pt 1)(1):1-6.
Source: PubMed

ABSTRACT Hematopoietic stem cells have typically been defined as pluripotent cells with self-renewal capacity. Recent studies have shown striking differences in the mean length of telomeric repeat sequences at the end of chromosomes from human hematopoietic cells at different stages of development. The most likely explanation for these observations is that hematopoietic stem cells, like all other somatic cells studied to date, lose telomeric DNA upon each cell division. In this review, limitations in the replicative potential of hematopoietic stem cells are discussed in the context of possible clinical use of such cells for transplantation and gene therapy.

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    • "During DNA replication, the linear ends of chromosomes are eroded at each cell division due to the end replication problem.1 Telomeres, the very ends of linear chromosomes, are predominantly composed of tandem repeats of short sequences; in vertebrates, the repeats consist of the TTAGGG hexanucleotide.2 Telomere lengths are also remarkably heterogeneous among individuals and vary according to the origin, age, and proliferative history of cells.3,4 Telomere length variations among individuals of the same age are, therefore, thought to be related to variations in ageing and longevity.5 "
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    ABSTRACT: Telomerase reverse transcriptase (TERT) is the protein component of telomerase and combined with an RNA molecule, telomerase RNA component, forms the telomerase enzyme responsible for telomere elongation. Telomerase is essential for maintaining telomere length from replicative attrition and thus contributes to the preservation of genome integrity. Although diverse mouse models have been developed and studied to prove the physiological roles of telomerase as a telomere- elongating enzyme, recent studies have revealed non-canonical TERT activities beyond telomeres. To gain insights into the physiological impact of extra-telomeric roles, this review revisits the strategies and phenotypes of telomerase mouse models in terms of the extra-telomeric functions of telomerase.
    Yonsei medical journal 01/2014; 55(1):1-8. DOI:10.3349/ymj.2014.55.1.1 · 1.26 Impact Factor
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    • ") were seeded in triplicate in 96-well plates (Nalgene Nunc) and cultured in serum depleted media containing various growth factors. The serum-deprived media is a modification of the serum-deprived media developed for growth of haematopoietic progenitors (Migliaccio et al., 1988; Lansdorp, 1995) and adapted for the growth of stromal progenitors (Gronthos and Simmons, 1995). Cells were incubated for 5 days with the following growth factors at 10–100 ng/ml: recombinant human BMP-2 (Cytolab/Peprotech, Rehovot, Israel), BMP-7 (Stryker Biotech, St Leonards, NSW, Australia), recombinant human EGF (Peprotech, Rocky Hill, NJ) recombinant human IGF-1 (Gropep, Thebarton, SA, Australia), recombinant human FGF-2 (Cytolab/Peprotech), recombinant human PDGF-BB (Peprotech), recombinant human TGF-b1 (Cytolab/Peprotech), recombinant human TGF-b3 (Cytolab/Peprotech), recombinant human TGF-a (Peprotech). "
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    ABSTRACT: Since discovery, significant interest has been generated in the potential application of mesenchymal stem cells or multipotential stromal cells (MSC) for tissue regeneration and repair, due to their proliferative and multipotential capabilities. Although the sheep is often used as a large animal model for translating potential therapies for musculoskeletal injury and repair, the characteristics of MSC from ovine bone marrow have been inadequately described. Histological and gene expression studies have previously shown that ovine MSC share similar properties with human and rodents MSC, including their capacity for clonogenic growth and multiple stromal lineage differentiation. In the present study, ovine bone marrow derived MSCs positively express cell surface markers associated with MSC such as CD29, CD44 and CD166, and lacked expression of CD14, CD31 and CD45. Under serum-deprived conditions, proliferation of MSC occurred in response to EGF, PDGF, FGF-2, IGF-1 and most significantly TGF-alpha. While subcutaneous transplantation of ovine MSC in association with a ceramic HA/TCP carrier into immunocomprimised mice resulted in ectopic osteogenesis, adipogenesis and haematopoietic-support activity, transplantation of these cells within a gelatin sponge displayed partial chondrogenesis. The comprehensive characterisation of ovine MSC described herein provides important information for future translational studies involving ovine MSC.
    Journal of Cellular Physiology 05/2009; 219(2):324-33. DOI:10.1002/jcp.21670 · 3.87 Impact Factor
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    • "In this method, the intensity of the fluorescent signal has been demonstrated to be directly proportional to telomere length as measured by Southern blot (Lansdorp, 1995). The fluorescent signals were visualized under an epifluorescence microscope (axiophot; Zeiss, Le Pecq, France) equipped with a computer-driven filter wheel and a Zeiss 100-watt fluorescence lamp. "
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    ABSTRACT: To evaluate the incidence and the predictive signs of therapy-related myelodysplasia and/or acute myeloid leukaemia (tMDS/tAML), we undertook a prospective study over a 4-year period of 221 patients who underwent autologous haematopoietic progenitor cell transplantation. Only seven patients (3.1%) were identified to have tMDS/tAML. Peripheral cytopenia was the first sign; diagnosis could be achieved by cytological analysis of bone marrow smears using World Health Organization criteria. All patients presented with bi- or trilineage dysplasia. Haematopoietic reconstitution was significantly delayed in patients progressing to tMDS/tAML compared with the control group. Typical cytogenetic abnormalities were observed in five of seven patients. The mean time interval between transplantation and cytological diagnosis, or detection of cytogenetic abnormalities, was 20.0 months and 31.2 months respectively. Pantelomeric fluorescence analysis using quantitative fluorescence in situ hybridization enabled us to make two major observations: (i) the fluorescence intensity in metaphases of all autografted patients was weak, and highly variable between tMDS patients; (ii) a drastic reduction of the telomere fluorescence intensity was observed in two patients who rapidly evolved to acute leukaemia. In conclusion, early detection of tMDS/tAML could be achieved by close follow-up of the bone marrow repopulation, and confirmed by cytological bone marrow examination and cytogenetic study. Our results address the implication of several factors, such as the initial telomeric status, and the effect of cytogenetic abnormalities and clonal expansion on bone marrow repopulation.
    British Journal of Haematology 08/2003; 122(1):109-17. DOI:10.1046/j.1365-2141.2003.04388.x · 4.96 Impact Factor
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