Parallel Hematopoietic Stem Cell Division Rate Estimation Using an Agent-Based Model on the Grid

2011 ◽  
Author(s):  
Richard C. van der Wath ◽  
Elizabeth C. van der Wath ◽  
Pietro Lio
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Hematopoietic Stem Cell ◽  
Agent Based Model ◽  
Division Rate ◽  
Hematopoietic Stem ◽  
Agent Based ◽  
Rate Estimation ◽  
Cell Division Rate ◽  
Stem Cell Division

Plerixafor Abrogates the Supportive Function of MSC for Self-Renewal of Human Hematopoietic Stem Cells,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3408-3408
Author(s):  
Annette Ludwig ◽  
Rainer Saffrich ◽  
Volker Eckstein ◽  
Angela Lenze ◽  
Anke Diehlmann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Division ◽  
Feeder Layer ◽  
Division Rate ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Division Rate ◽  
Cd34 Cells ◽  
Supportive Function

Abstract Abstract 3408 The CXCR4-SDF1α axis plays an important role in maintaining the stemness of human hematopoietic stem cells (HSC). In the present study we established a surrogate model for the bone marrow niche by culturing HSC on a feeder-layer of human mesenchymal stromal cells (MSC) and investigated the proliferation and differentiation behaviour upon perturbation by Plerixafor. HSC (CD34+ cells) were isolated from umbilical cord blood by fluorescent activated cell sorting (FACS). MSC were derived from bone marrow aspirates from healthy voluntary donors. HSC were stained with carboxyfluorescein succinimidyl ester (CFSE) and cultured on MSC feeder-layer for 6 days. For evaluating the influence of the culture medium on MSC cultures, three different media conditions (M1-M3) were used. Medium 1 (M1) contained 2% fetal calf serum (FCS), medium 2 (M2) contained 10% FCS and medium 3 (M3) contained GMP-grade human platelet lysate (hPL). Proliferation of HSC was calculated by analyzing the distribution of the CFSE dye (measured at day 1 and day 6). Plerixafor was added in concentrations of 0.1, 1.0 and 10.0 μM. On day 6, HSCs were harvested and analyzed by flow cytometry for CD34, CD38 and CXCR4 expressions in relationship to the cell division rate. When co-cultured with MSC, the division kinetics of HSC was increased, while the proportion of CD34+ cells remained significantly higher compared to HSC without MSC. Accordingly, more CD38− HSC were found after 6 days upon co-culture with MSC. All three MSC preparations supported self-renewing proliferation of HSC, whereas MSC M1 induced the strongest effect. This underlines that co-culture with MSC has a significant supportive function for hematopoiesis. The additional exposure to Plerixafor in the co-culture system partially reversed this effect in a dose-dependent manner: division rate of HSC and the proportion of CD34+ and CD38− cells were reduced with higher concentrations of Plerixafor. The reduction of self-renewing proliferation by Plerixafor was not observed in controls consisting of HSC without MSC. Plerixafor also rendered the CXCR4 receptors undetectable on the surface of CD34+ cells for up to 6 days, most probably due to a persisting blockade of the antibody-binding site. Human HSC co-cultured with MSC showed an increased cell division rate and produced a higher proportion of CD34+/CD38− cells. Different MSC culture media were systematically analysed in this setting and subtle differences in the supportive function could be observed. The addition of Plerixafor neutralized the effects of MSC, leading to an earlier loss of “stemness” and to lineage-commitment of HSC, thus providing evidence for the role of the CXCR4/SDF1α axis in terms of supportive function of MSC for self-renewal of HSC. Disclosures: Ho: Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 503-514 ◽  
Author(s):  
D.N. Cox ◽  
A. Chao ◽  
H. Lin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Germline Stem Cell ◽  
Dual Function ◽  
Germline Stem Cells ◽  
Division Rate ◽  
Germline Expression ◽  
A Cell ◽  
Stem Cell Division

piwi represents the first class of genes known to be required for stem cell self-renewal in diverse organisms. In the Drosophila ovary, piwi is required in somatic signaling cells to maintain germline stem cells. Here we show that piwi encodes a novel nucleoplasmic protein present in both somatic and germline cells, with the highly conserved C-terminal region essential for its function. Removing PIWI protein from single germline stem cells significantly decreases the rate of their division. This suggests that PIWI has a second role as a cell-autonomous promoter of germline stem cell division. Consistent with its dual function, over-expression of piwi in somatic cells causes an increase both in the number of germline stem cells and the rate of their division. Thus, PIWI is a key regulator of stem cell division - its somatic expression modulates the number of germline stem cells and the rate of their division, while its germline expression also contributes to promoting stem cell division in a cell-autonomous manner.

Caregiver perspectives on psychosocial care in pediatric hematopoietic stem cell transplantation (HCT).

2020 ◽  
Vol 8 (1) ◽  
pp. 67-78 ◽  
Author(s):  
Anne E. Kazak ◽  
Avi Madan Swain ◽  
Ahna L. H. Pai ◽  
Kimberly Canter ◽  
Olivia Carlson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Psychosocial Care ◽  
Hematopoietic Stem
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