Wnt1 Accelerates anEx VivoExpansion of Human Cord Blood CD34+CD38−Cells

Chotinantakul, Kamonnaree; Prasajak, Patcharee; Leeanansaksiri, Wilairat

doi:10.1155/2013/909812

Cited by 13 publications

(10 citation statements)

References 47 publications

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“…Neutrophils are essential for the innate immune response and can protect patients from bacterial infections in the initial phase of transplantation, especially for patients undergoing myelosuppressive chemotherapy [38,39]. Therefore, the capability to generate matured blood cells is also critical for stem cell transplantation [11,40].…”

Section: Discussionmentioning

confidence: 99%

“…6). To compensate for the limitation of AKTi in human HSPC expansion, other factors, including Wnt activator [38,41,42], should be used in combination with AKTi. We expect that the combination of AKTi and the activator of canonical Wnt signaling will promote the ex vivo expansion of functional HSPCs without affecting their differentiation capability (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacological inhibition of AKT activity in human CD34+ cells enhances their ability to engraft immunodeficient mice

Chen

Gao

Kobayashi

et al. 2017

Experimental Hematology

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Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplantation remains limited by the inability to expand functional HSCs ex vivo. To determine the role of phosphoinositide 3-kinase (PI3K)/AKT signaling in human hematopoietic stem and progenitor cell (HSPC) maintenance, we examined the effect of genetic and pharmacological inhibition of AKT on human umbilical cord blood (UCB) CD34+ cells. We found that knock-down of AKT1 in human UCB CD34+ cells using short interfering RNAs targeting AKT1 enhances their quiescence and colony formation potential in vitro. We treated human UCB CD34+ cells with an AKT-specific inhibitor (AKTi) and performed both in vitro and in vivo stem and progenitor cell assays. We found that ex vivo treatment of human HSPCs maintains CD34 expression and enhances colony formation in serial replating assays. Moreover, pharmacological inhibition of AKT enhances the short-term repopulating potential of human UCB CD34+ cells in immunodeficient mice. Mechanistically, genetic and pharmacological inhibition of AKT activity promotes human HSPC quiescence. These preclinical results suggest a positive role for AKTi during ex vivo culture of human UCB HSPCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of AKT activity in human CD34+ cells enhances their ability to engraft immunodeficient mice

Chen

Gao

Kobayashi

et al. 2017

Experimental Hematology

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“…Recently, it has been demonstrated that the miRNA-320 family suppresses stem cell-like characteristics in prostate cancer cells by down-regulating the Wnt/beta-catenin signaling pathway [ 49 ]—a pathway which is also of central importance for regulation of self-renewal and proliferation in hematopoietic stem cells [ 50 , 51 ]. Furthermore, miRNA-320 targets the transferrin receptor CD71 in the human leukemia cell line HL-60, thereby inhibiting proliferation [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells

et al. 2015

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Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34+ hematopoietic stem and progenitor cells (HSPCs) – however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs) or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy – particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate) increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration.

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“…21 , 22 Many research groups have developed an ex vivo culture procedure that results in the further expansion of CD34 + cells resulting in more rapid engraftment of neutrophils following infusion to transplant recipients. 23 …”

Section: Discussionmentioning

confidence: 99%

Impact of maternal and neonatal factors on parameters of hematopoietic potential in umbilical cord blood

Al-Deghaither

2015

SMJ

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Objectives:To determine characteristics of laboratory parameters of hematopoietic potential in umbilical cord blood and their association with maternal and neonatal factors.Methods:This prospective analysis was performed on 206 umbilical cord blood donations (50-200 ml) from King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia between January and September 2014. Samples were processed and analyzed for total nucleated cells (TNC’s), cluster designation (CD)45+, CD34+ counts, nucleated red blood cells (NRBCs) count, and viability testing.Results:Most of the study participants (63.6%) were on their first 3 deliveries and from women with age between 17 and 30 years (80.6%). The donated volume was 50.4-192.4 ml, TNCs ranged from 500.2×106 to 9430.3 ×106 cells, and CD34+ cells ranged from 1.25×106 to 12.82×106/unit. The volume was positively affected by bigger birth weight of the baby (p<0.0001), larger placenta (p=0.001), TNCs (p<0.0001), CD34+ (p<0.0001), NRBCs (p<0.0001), and viability (p=0.002). There were no statistically significant differences between baby boys and girls for laboratory variables.Conclusion:In the selection and identification of a possible donor of umbilical cord blood, several maternal and neonatal factors should be considered, as younger maternal age, neonatal birth weight >3300 grams, larger placental size, and first or second-born babies, were shown to be associated with higher TNCs, CD34+, CD45+, NRBCs, and viability.

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Wnt1 Accelerates anEx VivoExpansion of Human Cord Blood CD34⁺CD38⁻Cells

Cited by 13 publications

References 47 publications

Pharmacological inhibition of AKT activity in human CD34+ cells enhances their ability to engraft immunodeficient mice

Pharmacological inhibition of AKT activity in human CD34+ cells enhances their ability to engraft immunodeficient mice

MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells

Impact of maternal and neonatal factors on parameters of hematopoietic potential in umbilical cord blood

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