Overcoming TNF-α Induced Suppression of Erythroid Differentiation of Human Cord Blood CD34+ Cells with Arsenic Trioxide.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3451-3451
Author(s):  
Jong-Ho Won ◽  
Hee-Jeong Cheong ◽  
Sook-Ja Kim ◽  
Sang-Byung Bae ◽  
Chan-Kyu Kim ◽  
...  
Keyword(s):  
Cord Blood ◽  
Arsenic Trioxide ◽  
Erythroid Differentiation ◽  
Glycophorin A ◽  
Dependent Manner ◽  
Human Cord Blood ◽  
Colony Assay ◽  
Cd34 Cells ◽  
Tnf Α ◽  
Cord Blood Cd34

Abstract The anemia of chronic disease-which encompasses inflammation, infection, tissue injury, and conditions associated with the release of proinflammatory cytokines (such as cancer)- is one of the most common forms of anemia seen clinically. Symptomatic anemia requires treatment. The two major forms of treatment are transfusions and erythropoietin. Arsenic trioxide (As2O3) used to treat human diseases for centuries in traditional Chinese medicine. Our recent studies suggest that low dose of As2O3 induces erythroid differentiation of K562 human leukemic cells and high dose of As2O3 induce apoptosis. In this study, we have investigated in vitro effect of As2O3 on the erythroid differentiation and it could inhibit TNF-α induced suppression of erythroid differentiation of human cord blood CD34+ cells. Expression of glycophorin A was 35.94 ± 7.94% after 7 days culture of human cord blood CD34+ cells and was decreased to 17.63 ± 7.33% when culture of human cord blood CD34+ cells with 100ng/mL of TNF-α. Expression of glycophorin A was increased in dose dependent manner after 7 days treatment with As2O3 and As2O3 increased percentage of glycophorin A in culture with TNF-α compared to TNF-α alone. The results of colony assay of CFU-MIX and BFU-E after culture with various conditions revealed similar patterns with expression of glycophorin A. These results suggest that As2O3 induces erythroid differentiation of human cord blood CD34+ cells and can reverse TNF-α induced suppression of erythroid differentiation of human cord blood CD34+ cells. The BFU-E colony assay of the human cord blood CD34+ cells after culture with TNF-α or/and Arsenic trioxide. The BFU-E colony assay of the human cord blood CD34+ cells after culture with TNF-α or/and Arsenic trioxide.

The αIIbβ3 integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34+cord blood cells to megakaryocytes

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4169-4177 ◽  
Author(s):  
Adeline Lepage ◽  
Marylène Leboeuf ◽  
Jean-Pierre Cazenave ◽  
Corinne de la Salle ◽  
François Lanza ◽  
...  
Keyword(s):  
Cord Blood ◽  
Messenger Rna ◽  
Human Cord Blood ◽  
Cd34 Cells ◽  
Conditional Expression ◽  
Multistep Process ◽  
Cord Blood Cd34 ◽  
Specific Proteins ◽  
Cord Blood Cells

Abstract Megakaryocytopoiesis is a complex multistep process involving cell division, endoreplication, and maturation and resulting in the release of platelets into the blood circulation. Megakaryocytes (MK) progressively express lineage-restricted proteins, some of which play essential roles in platelet physiology. Glycoprotein (GP)Ib-V-IX (CD42) and GPIIb (CD41) are examples of MK-specific proteins having receptor properties essential for platelet adhesion and aggregation. This study defined the progressive expression of the GPIb-V-IX complex during in vitro MK maturation and compared it to that of GPIIb, an early MK marker. Human cord blood CD34+ progenitor cells were cultured in the presence of cytokines inducing megakaryocytic differentiation. GPIb-V-IX expression appeared at day 3 of culture and was strictly dependent on MK cytokine induction, whereas GPIIb was already present in immature CD34+ cells. Analysis by flow cytometry and of the messenger RNA level both showed that GPV appeared 1 day later than GPIb-IX. Microscopy studies confirmed the late appearance of GPV, which was principally localized in the cytoplasm when GPIb-IX was found on the cell surface, suggesting a delayed program of GPV synthesis and trafficking. Cell sorting studies revealed that the CD41+GPV+ population contained 4N and 8N cells at day 7, and was less effective than CD41+GPV− cells in generating burst-forming units of erythrocytes or MK colonies. This study shows that the subunits of the GPIb-V-IX complex represent unique surface markers of MK maturation. The genes coding for GPIb-IX and GPV are useful tools to study megakaryocytopoiesis and for tissue-specific or conditional expression in mature MK and platelets.

scholarly journals miR-17 promotes expansion and adhesion of human cord blood CD34+ cells in vitro

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuxia Yang ◽  
Saifeng Wang ◽  
Zhenchuan Miao ◽  
Wei Ma ◽  
Yanju Zhang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Human Cord Blood ◽  
Cd34 Cells ◽  
Cord Blood Cd34

scholarly journals Cell cycling status of human cord blood CD34+ cells during ex vivo expansion is related to the level of very late antigen expression

2001 ◽  
Vol 16 (1) ◽  
pp. 20 ◽  
Author(s):  
Ju Young Seoh ◽  
Hae Young Park ◽  
Wha Soon Chung ◽  
Seung Cheol Kim ◽  
Myong Joon Hahn ◽  
...  
Keyword(s):  
Cord Blood ◽  
Ex Vivo ◽  
Antigen Expression ◽  
Ex Vivo Expansion ◽  
Human Cord Blood ◽  
Cd34 Cells ◽  
Late Antigen ◽  
Cord Blood Cd34 ◽  
Cell Cycling

Delta-4 Notch ligand promotes erythroid differentiation of human umbilical cord blood CD34+ cells

2006 ◽  
Vol 34 (4) ◽  
pp. 424-432 ◽  
Author(s):  
Akira Sugimoto ◽  
Mayuko Yamamoto ◽  
Motoyuki Suzuki ◽  
Toshiya Inoue ◽  
Shuji Nakamura ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Erythroid Differentiation ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Notch Ligand ◽  
Cd34 Cells ◽  
Cord Blood Cd34

Ex-Vivo Expansion of Human Cord Blood CD34+ Cells by Overexpression of Bmi-1.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1329-1329
Author(s):  
Aleksandra Rizo ◽  
Edo Vellenga ◽  
Gerald de Haan ◽  
Jan Jacob Schuringa
Keyword(s):  
Cord Blood ◽  
Cell Expansion ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Human Cord Blood ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Cord Blood Cd34

Abstract Hematopoietic stem cells (HSCs) are able to self-renew and differentiate into cells of all hematopoietic lineages. Because of this unique property, they are used for HSC transplantations and could serve as a potential source of cells for future gene therapy. However, the difficulty to expand or even maintain HSCs ex vivo has been a major limitation for their clinical applications. Here, we report that overexpression of the Polycomb group gene Bmi-1 in human cord blood-derived HSCs can potentially overcome this limitation as stem/progenitor cells could be maintained in liquid culture conditions for over 16 weeks. In mouse studies, it has been reported that increased expression of Bmi-1 promotes HSC self-renewal, while loss-of-function analysis revealed that Bmi-1 is implicated in maintenance of the hematopoietic stem cells (HSC). In a clinically more relevant model, using human cord blood CD34+ cells, we have established a long-term ex-vivo expansion method by stable overexpression of the Bmi-1 gene. Bmi-1-transduced cells proliferated in liquid cultures supplemented with 20% serum, SCF, TPO, Flt3 ligand, IL3 and IL6 for more than 4 months, with a cumulative cell expansion of more then 2×105-fold. The cells remained cytokine-dependent, while about 4% continued to express CD34 for over 20 weeks of culture. The cultured cells retained their progenitor activity throughout the long-term expansion protocol. The colony-forming units (CFUs) were present at a frequency of ~ 30 colonies per 10 000 cells 16 weeks after culture and consisted of CFU-GM, BFU-E and high numbers of CFU-GEMM type progenitors. After plating the transduced cells in co-cultures with the stromal cell line MS5, Bmi-1 cells showed a proliferative advantage as compared to control cells, with a cumulative cell expansion of 44,9 fold. The non-adherent cells from the co-cultures gave rise to higher numbers of colonies of all types (~70 colonies/10.000 cells) after 4 weeks of co-culture. The LTC-IC frequencies were 5-fold higher in the Bmi-1-transduced cells compared to control cells (1/361 v.s. 1/2077, respectively). Further studies will be focused on in-vivo transplantation of the long-term cultured cells in NOD/SCID mice to test their repopulating capacity. In conclusion, our data implicate Bmi-1 as an important modulator of human HSC self-renewal and suggest that it can be a potential target for therapeutic manipulation of human HSCs.

scholarly journals Apoptosis and megakaryocytic differentiation during ex vivo expansion of human cord blood CD34+ cells using thrombopoietin

2001 ◽  
Vol 113 (2) ◽  
pp. 470-478 ◽  
Author(s):  
Kyung-Ha Ryu ◽  
Susan Chun ◽  
Steve Carbonierre ◽  
Seock-Ah Im ◽  
Hyung-Lae Kim ◽  
...  
Keyword(s):  
Cord Blood ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Human Cord Blood ◽  
Megakaryocytic Differentiation ◽  
Cd34 Cells ◽  
Cord Blood Cd34
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