English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells.

Arulmozhivarman, G., Kräter, M., Wobus, M., Friedrichs, J., Bejestani, E. P., Müller, K., et al. (2017). Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells. Scientific reports, 7(1): 12084. doi:10.1038/s41598-017-12360-0.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Arulmozhivarman, Guruchandar, Author
Kräter, Martin, Author
Wobus, Manja, Author
Friedrichs, Jens1, Author           
Bejestani, Elham Pishali, Author
Müller, Katrin, Author
Lambert, Katrin, Author
Alexopoulou, Dimitra, Author
Dahl, Andreas, Author
Stöter, Martin1, Author           
Bickle, Marc1, Author           
Shayegi, Nona, Author
Hampe, Jochen, Author
Stölzel, Friedrich, Author
Brand, Michael1, Author           
Bonin, Malte von, Author
Bornhäuser, Martin, Author
Affiliations:
1Max Planck Institute for Molecular Cell Biology and Genetics, ou_2340692              

Content

show
hide
Free keywords: -
 Abstract: The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice. Interestingly, VPA increased CD34(+) cell adhesion to primary mesenchymal stromal cells and reduced their in vitro chemokine-mediated migration capacity. In line with this, VPA-treated human CD34(+) cells showed reduced homing and early engraftment in a xenograft transplant model, but retained their long-term engraftment potential in vivo, and maintained their differentiation ability both in vitro and in vivo. In summary, our data demonstrate that certain HDACIs lead to a net expansion of hHSPCs with retained long-term engraftment potential and could be further explored as candidate compounds to amplify ex-vivo engineered peripheral blood stem cells.

Details

show
hide
Language(s):
 Dates: 2017-09-21
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41598-017-12360-0
Other: cbg-6953
PMID: 28935977
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Scientific reports
  Other : Sci Rep
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 7 (1) Sequence Number: 12084 Start / End Page: - Identifier: -