In Vitro Proliferation, Expansion, and Differentiation of a CD34+ Cell-Enriched Hematopoietic Cell Population from Human Umbilical Cord Blood in Response to Recombinant Cytokines

Flores-Guzmán, Patricia; Gutiérrez-Rodrı́guez, Margarita; Mayani, Héctor

doi:10.1016/s0188-4409(01)00368-x

Cited by 56 publications

(33 citation statements)

References 27 publications

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“…S6A). We focused our attention on G-CSF and IL-6, as these cytokines were previously shown to be important for the differentiation and proliferation of myeloid cells (16,17). We validated the Polyphenon E-induced secretion of the G-CSF and IL-6 by ELISA (not shown).…”

Section: Resultsmentioning

confidence: 99%

Polyphenol E Enhances the Antitumor Immune Response in Neuroblastoma by Inactivating Myeloid Suppressor Cells

Santilli

Piotrowska

Cantilena

et al. 2013

Clinical Cancer Research

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Purpose: Neuroblastoma is a rare childhood cancer whose high risk, metastatic form has a dismal outcome in spite of aggressive therapeutic interventions. The toxicity of drug treatments is a major problem in this pediatric setting. In this study, we investigated whether Polyphenon E, a clinical grade mixture of green tea catechins under evaluation in multiple clinical cancer trials run by the National Cancer Institute (Bethesda, MD), has anticancer activity in mouse models of neuroblastoma.Experimental Design: We used three neuroblastoma models: (i) transgenic TH-MYCN mouse developing spontaneous neuroblastomas; (ii) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenotransplanted with human SHSY5Y cells; and (iii) A/J mice transplanted with syngeneic Neuro 2A cells. Mice were randomized in control and Polyphenon E-drinking groups. Blood from patients with neuroblastoma and normal controls was used to assess the phenotype and function of myeloid cells.Results: Polyphenon E reduced the number of tumor-infiltrating myeloid cells, and inhibited the development of spontaneous neuroblastomas in TH-MYCN transgenic mice. In therapeutic models of neuroblastoma in A/J, but not in immunodeficient NOD/SCID mice, Polyphenon E inhibited tumor growth by acting on myeloid-derived suppressor cells (MDSC) and CD8 T cells. In vitro, Polyphenon E impaired the development and motility of MDSCs and promoted differentiation to more neutrophilic forms through the 67 kDa laminin receptor signaling and induction of granulocyte colony-stimulating factor. The proliferation of T cells infiltrating a patient metastasis was reactivated by Polyphenon E.Conclusions: These findings suggest that the neuroblastoma-promoting activity of MDSCs can be manipulated pharmacologically in vivo and that green tea catechins operate, at least in part, through this mechanism.

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Section: Resultsmentioning

confidence: 99%

Polyphenol E Enhances the Antitumor Immune Response in Neuroblastoma by Inactivating Myeloid Suppressor Cells

Santilli

Piotrowska

Cantilena

et al. 2013

Clinical Cancer Research

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“…After CC-4047 stimulation, secretion of G-CSF increased within 24 hours 10-fold in comparison with control cells. Because G-CSF mediates enhanced development of myeloid progenitors, 24 our data suggest that especially the up-regulation of G-CSF contributes to enhanced myelopoiesis. MCP-1, which is known to support predominantly the granulocytic lineage 25 and to augment the clonal expansion of progenitor cells, 26 increased also up to 500% on day 1 under CC-4047 treatment as compared with control.…”

Section: Discussionmentioning

confidence: 74%

Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis

Koh

Janz

Mapara

et al. 2005

Blood

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Immunomodulatory derivative (IMiD) CC-4047, a new analog of thalidomide, directly inhibits growth of B-cell malignancies in vivo and in vitro and exhibits stronger antiangiogenic activity than thalidomide. However, there is little information on whether CC-4047 affects normal hematopoiesis. Here we investigated the effect of CC-4047 on lineage commitment and differentiation of hematopoietic stem cells. We found that CC-4047 effectively inhibits erythroid cell colony formation from CD34 ؉ cells and increases the frequency of myeloid colonies. We also demonstrate that development of both erythropoietin-independent and erythropoietindependent red cell progenitors was strongly inhibited by CC-4047, while terminal red cell differentiation was unaffected. DNA microarray analysis revealed that red cell transcription factors, including GATA-1, GATA-2, erythroid Kruppellike factor (EKLF), and growth factor independence-1B (Gfi-1b), were downregulated in CC

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“…34,55 Given our results on the differentiationpromoting effects of thyroid hormone and numerous reports on similar effects of transforming growth factor ␤ (TGF-␤), 56-58 it may well be that the absence of these serum components from the synthetic StemSpan medium was critical for achieving long-term proliferation of erythroid progenitors. Compared with other current procedures, it should also be noted that our conditions did not require positive preselection for immature, pluripotent progenitors (eg, CD34 ϩ /c-Kit Ϫ ), 55,59 negative selection (depletion) against lymphoid or granulocytic cells nor highly complex mixtures of multiple cytokines. 60 Importantly, the use of serum-free medium yielded immature erythroid progenitors with an in vitro lifespan approaching the "Hayflick Limit" of human fibroblasts (40-50 generations).…”

Section: Discussionmentioning

confidence: 99%

Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors

Leberbauer

Boulmé

Unfried

et al. 2005

Blood

168

143

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Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation factors, were obtained within 8 days from a starting population of mature and immature mononuclear cells. Due to previous results in mouse and chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was not unexpected. Surprisingly, however, androgen had a positive effect on the sustained expansion of human female but not male erythroid progenitors. Under optimal conditions, sustained proliferation of erythroid progenitors resulted in a more than 10 9 -fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone ( IntroductionHematopoietic development within the erythroid lineage requires a delicate balance between the opposing effects of proliferationpromoting factors maintaining the renewal capacity of immature erythroid progenitors and differentiation-inducing factors required for successful terminal maturation of erythroid progenitors into red blood cells. 1 In adult humans, erythroid differentiation produces about 2 ϫ 10 11 (roughly 20 g) red cells per day, representing the most vigorous proliferation process in the entire body. Because low numbers of erythrocytes are immediately life-threatening, erythropoiesis needs regulatory mechanisms temporarily altering the balance toward enhanced proliferation to cope with stress situations such as low oxygen levels at elevated altitudes (hypoxia) or massive blood loss.In vivo, both renewal and maturation of human erythroid progenitors proceed in parallel in the bone marrow. It has thus been difficult to assess the contribution of particular signaling pathways and their deregulation during aberrant depletion of these progenitors, or their death on differentiation in anemia, versus unscheduled progenitor proliferation (as occurring in leukemogenesis). Most information was obtained from established cell lines and, more recently, primary animal cell models of chicken and mouse in defined media. [1][2][3] The latter approach even allowed analysis of cells from genetically modified mice. [4][5][6] For sustained proliferation, both avian and murine primary erythroblasts require cooperation between erythropoietin (Epo), stem cell factor (SCF), and glucocorticoids (dexamethasone [Dex]). Involvement of Epo and SCF was expected from their contribution to proliferation and survival of erythroid cells, 7-9 whereas the stress hormone Dex massively prolonged progenitor proliferation (from 10 to 30 days in chickens, 7 to 20 days in mice), at the same time reducing their rate of spontaneous differentiation. Our idea that this might point to specific roles for glucocorticoids in stress erythropoiesis could be verified in vivo using mutant mice carrying a dimerizationdefective glucoco...

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In Vitro Proliferation, Expansion, and Differentiation of a CD34+ Cell-Enriched Hematopoietic Cell Population from Human Umbilical Cord Blood in Response to Recombinant Cytokines

Cited by 56 publications

References 27 publications

Polyphenol E Enhances the Antitumor Immune Response in Neuroblastoma by Inactivating Myeloid Suppressor Cells

Polyphenol E Enhances the Antitumor Immune Response in Neuroblastoma by Inactivating Myeloid Suppressor Cells

Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis

Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors

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