The Effect Of Poly(I:C) And 5-Fluorouracil On Hsc And Endothelial Cell Cycle Activation Following An 8-Day Recovery Period

Jacob Rabinovitch

School Name

Governor's School for Science and Math

Grade Level

12th Grade

Presentation Topic

Physiology and Health

Presentation Type

Mentored

Mentor

Mentor: Dr. Sohn; Department of Stem Cells and Cancer, German Cancer Research Center

Oral Presentation Award

2nd Place

Abstract

A proper functioning blood system relies upon the self-renewal and differentiation capabilities of hematopoietic stem cells (HSC’s). In response to inflammation, the cell releases various cytokines, for example interferon-alpha (IFNα), which signal to HSC’s to exit a state of quiescence and enter the cell cycle. This work examined the recovery of bone marrow after 8 days rest following the induced activation of HSC’s by the interferon mimetic poly(I:C), and chemotherapeutic treatment by the drug 5-fluorouracil (5-FU), which alone leads to massive cell death. Mice were injected with poly(I:C), which effectively stimulates dormant HSC’s such that they can be targeted with 5-FU. Following a double injection of 5-FU and poly(I:C), the animals were allowed a recovery period and their bone marrow was harvested. Cells were then quantified, immunostained, and measured using flow cytometry. The results indicate that bone marrow tissue is able to partially recover following 8 days. This is indicated by an approximate 77% decrease in Sca-1 expression in endothelial cells from mice co-treated with poly(I:C) and 5-FU than in endothelial cells from mice treated with 5-FU alone. This supports the hypothesis that there is a relationship between hematopoietic stem cells and their endothelial niche, which has implications regarding blood vessel growth following inflammation.

Location

Owens 107

Start Date

4-16-2016 11:15 AM

COinS
 
Apr 16th, 11:15 AM

The Effect Of Poly(I:C) And 5-Fluorouracil On Hsc And Endothelial Cell Cycle Activation Following An 8-Day Recovery Period

Owens 107

A proper functioning blood system relies upon the self-renewal and differentiation capabilities of hematopoietic stem cells (HSC’s). In response to inflammation, the cell releases various cytokines, for example interferon-alpha (IFNα), which signal to HSC’s to exit a state of quiescence and enter the cell cycle. This work examined the recovery of bone marrow after 8 days rest following the induced activation of HSC’s by the interferon mimetic poly(I:C), and chemotherapeutic treatment by the drug 5-fluorouracil (5-FU), which alone leads to massive cell death. Mice were injected with poly(I:C), which effectively stimulates dormant HSC’s such that they can be targeted with 5-FU. Following a double injection of 5-FU and poly(I:C), the animals were allowed a recovery period and their bone marrow was harvested. Cells were then quantified, immunostained, and measured using flow cytometry. The results indicate that bone marrow tissue is able to partially recover following 8 days. This is indicated by an approximate 77% decrease in Sca-1 expression in endothelial cells from mice co-treated with poly(I:C) and 5-FU than in endothelial cells from mice treated with 5-FU alone. This supports the hypothesis that there is a relationship between hematopoietic stem cells and their endothelial niche, which has implications regarding blood vessel growth following inflammation.