Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication

Gammaitoni, Loretta; Weisel, Katja; Gunetti, Monica; Wu, Kai Da; Bruno, Stefania; Pinelli, Silvana; Bonati, Antonio; Aglietta, Massimo; Moore, Malcolm A.S.; Piacibello, Wanda

doi:10.1182/blood-2003-09-3079

Cited by 76 publications

(56 citation statements)

References 28 publications

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“…52 However, it is notable that a recent investigation demonstrated long-term maintenance of TL in CD34 þ cells cultured under specific self-renewal conditions. 43 TL is also maintained in telomerase-positive immortal leukemia cell lines. Clearly, further investigation into the positive and negative regulators of TL in hematopoietic cells is warranted.…”

Section: Discussionmentioning

confidence: 96%

“…Telomere loss in STF6 most likely reflected TL changes in differentiating (CD34À) cells, as a previous study demonstrated long-term maintenance of TL in CD34 þ cells that were FACS sorted from STF6 expansion cultures. 43 Irrespective of those data, the results shown here demonstrate that the mean TL of CB cells expanded for 7 days in STF can be used as a surrogate for the TL of unexpanded CD34 þ cells.…”

Section: Expansion Without Net Telomere Loss During Culture In Stf Bmentioning

confidence: 95%

“…Both of these cytokine combinations were previously shown to expand CBderived HPCs without apparent loss of long-term proliferative potential. 43,44 Furthermore, STF6 was shown to promote longterm expansion of primitive HPCs with minimal telomere loss. 43 In our hands, there was no significant difference in total cell expansion in STF (mean ¼ 5.0270.…”

Section: Expansion Without Net Telomere Loss During Culture In Stf Bmentioning

confidence: 99%

“…43,44 Furthermore, STF6 was shown to promote longterm expansion of primitive HPCs with minimal telomere loss. 43 In our hands, there was no significant difference in total cell expansion in STF (mean ¼ 5.0270. (Figure 1a and b).…”

Section: Expansion Without Net Telomere Loss During Culture In Stf Bmentioning

confidence: 99%

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Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential

2007

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Excessive telomere shortening has been demonstrated in inherited and acquired blood disorders, including aplastic anemia and myelodysplastic syndromes. It is possible that replicative exhaustion, owing to critical telomere shortening in hematopoietic progenitor cells (HPCs), contributes to the development of cytopenias in these disorders. However to date, a direct link between the telomere length (TL) of human HPCs and their proliferative potential has not been demonstrated. In the present investigation, the TL and level of telomerase enzyme activity (TA) detected in cord blood (CB)-derived HPCs was found to predict erythroid expansion (Po0.01 and P ¼ 0.01 respectively). These results were corroborated by a correlation between proliferation of erythroid cells and telomere loss (P ¼ 0.01). In contrast, no correlations were found between initial TL, telomere loss or TA and the expansion of other myeloid lineagecommitted cells. There was also no correlation between TL or TA and the number of clonogenic progenitors, including primitive progenitors derived from long-term culture. Our investigations revealed upregulation of telomerase to tumor cell levels in CD34À cells undergoing erythroid differentiation. Together, these results provide new insight into the regulation of TL and TA during myeloid cell expansion and demonstrate that TL is an important determinant of CB-derived erythroid cell proliferation. Leukemia (2007) 21, 983-991.

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Section: Discussionmentioning

confidence: 96%

Section: Expansion Without Net Telomere Loss During Culture In Stf Bmentioning

confidence: 95%

Section: Expansion Without Net Telomere Loss During Culture In Stf Bmentioning

confidence: 99%

Section: Expansion Without Net Telomere Loss During Culture In Stf Bmentioning

confidence: 99%

See 2 more Smart Citations

Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential

2007

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“…In addition the combination of FL and TPO may prevent apoptosis 60 and support the self-renewal of primitive stem cells by preventing telomere degradation. 61 …”

Section: Cytokinesmentioning

confidence: 99%

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

Hofmeister

Zhang

Knight

et al. 2006

Bone Marrow Transplant

200

172

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Umbilical cord blood transplantation (UCBT) in adults is limited by the small number of primitive hematopoietic stem cells (HSC) in each graft, resulting in delayed engraftment post transplant, and both short-and longterm infectious complications. Initial efforts to expand UCB progenitors ex vivo have resulted in expansion of mature rather than immature HSC, confounded by the inability to accurately and reliably measure long-term reconstituting cells. Ex vivo expansion of UCB HSC has failed to improve engraftment because of resulting defects that promote apoptosis, disrupt marrow homing and initiate cell cycling. Here we discuss the future of ex vivo expansion, which we suggest will include the isolation of immature hematopoietic progenitors on the basis of function rather than surface phenotype and will employ both cytokines and stroma to maintain and expand the stem cell niche. We suggest that ex vivo expansion could be enhanced by manipulating newly discovered signaling pathways (Notch, Wnt, bone morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular mediators (phosphatase and tensin homolog and glycogen synthase kinase-3) in a manner that promotes HSC expansion with less differentiation. Improved methods for ex vivo expansion will make UCBT available to more patients, decrease engraftment times and allow more rapid immune reconstitution post transplant.

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Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

Costa

Soure

Cabral

et al. 2017

Biotechnology Journal

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The adult bone marrow (BM) niche is a complex entity where a homeostatic hematopoietic system is maintained through a dynamic crosstalk between different cellular and non-cellular players. Signaling mechanisms triggered by cell-cell, cell-extracellular matrix (ECM), cell-cytokine interactions, and local microenvironment parameters are involved in controlling quiescence, self-renewal, differentiation, and migration of hematopoietic stem/progenitor cells (HSPC). A promising strategy to more efficiently expand HSPC numbers and tune their properties ex vivo is to mimic the hematopoietic niche through integration of adjuvant stromal cells, soluble cues, and/or biomaterial-based approaches in HSPC culture systems. Particularly, mesenchymal stem/stromal cells (MSC), through their paracrine activity or direct contact with HSPC, are thought to be a relevant niche player, positioning HSPC-MSC co-culture as a valuable platform to support the ex vivo expansion of hematopoietic progenitors. To improve the clinical outcome of hematopoietic cell transplantation (HCT), namely when the available HSPC are present in a limited number such is the case of HSPC collected from umbilical cord blood (UCB), ex vivo expansion of HSPC is required without eliminating the long-term repopulating capacity of more primitive HSC. Here, we will focus on depicting the characteristics of co-culture systems, as well as other bioengineering approaches to improve the functionality of HSPC ex vivo.

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Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication

Cited by 76 publications

References 28 publications

Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential

Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

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