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Angptl4 maintains in vivo repopulation capacity of CD34(+) human cord blood cells.

Blank Savukinas, Ulrika LU ; Ehrnström, Birgitta; Heinz, Niels; Nilsson, Eva C LU ; Brun, Ann; Baum, Christopher; Schiedlmeier, Bernhard and Karlsson, Stefan LU (2012) In European Journal of Haematology 89(3). p.198-205
Abstract
OBJECTIVES:

Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass an attractive approach that would substantially broaden the clinical applicability of HSCs derived from cord blood. Recently, members of the Angiopoietin-like (Angptl) family of growth factors were shown to expand both murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion of human NOD-SCID-repopulating cells (SRCs) ex vivo. Here, we sought to evaluate the potential of additional Angptls to expand human SRCs from cord blood. Additionally, the purpose of this study was to evaluate the reproducibility of Angptl-mediated expansion of SRCs across independent experiments.



METHODS:

Human CD34(+) cells... (More)
OBJECTIVES:

Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass an attractive approach that would substantially broaden the clinical applicability of HSCs derived from cord blood. Recently, members of the Angiopoietin-like (Angptl) family of growth factors were shown to expand both murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion of human NOD-SCID-repopulating cells (SRCs) ex vivo. Here, we sought to evaluate the potential of additional Angptls to expand human SRCs from cord blood. Additionally, the purpose of this study was to evaluate the reproducibility of Angptl-mediated expansion of SRCs across independent experiments.



METHODS:

Human CD34(+) cells from cord blood were cultured in vitro for eleven or eight days in the presence or absence of Angptls. The reconstitution capacity of expanded cells was subsequently measured in vivo by transplantation into NOD-SCID or NSG mice, and compared to that of uncultured cells.



RESULTS:

We report here that Angptl4 functions to maintain SRC-activity of CD34(+) CB-derived cells ex vivo as assayed in NOD-SCID and NSG mice. However, all Angptls tested, including Angptl1, 4, and 5, were associated with variation between experiments.



CONCLUSION:

Our findings indicate that Angptl4 and Angptl5 can lead to increased engraftment capacity of SRCs, but more frequently these factors are associated with maintenance of SRC-activity during ex vivo culture. Thus, Angptl-mediated expansion of SRCs ex vivo is associated with more inter-experimental variation than previously thought. We conclude that Angptls would be useful in instances where there is a need to maintain HSCs ex vivo, such as during transduction for gene therapy applications. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Haematology
volume
89
issue
3
pages
198 - 205
publisher
Wiley-Blackwell
external identifiers
  • wos:000307476800002
  • pmid:22639947
  • scopus:84865114664
ISSN
1600-0609
DOI
10.1111/j.1600-0609.2012.01812.x
language
English
LU publication?
yes
id
adfd8655-d04c-4449-86fc-53134906cf13 (old id 2608393)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22639947?dopt=Abstract
date added to LUP
2012-06-04 18:14:26
date last changed
2017-04-30 15:38:43
@article{adfd8655-d04c-4449-86fc-53134906cf13,
  abstract     = {OBJECTIVES: <br/><br>
Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass an attractive approach that would substantially broaden the clinical applicability of HSCs derived from cord blood. Recently, members of the Angiopoietin-like (Angptl) family of growth factors were shown to expand both murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion of human NOD-SCID-repopulating cells (SRCs) ex vivo. Here, we sought to evaluate the potential of additional Angptls to expand human SRCs from cord blood. Additionally, the purpose of this study was to evaluate the reproducibility of Angptl-mediated expansion of SRCs across independent experiments. <br/><br>
<br/><br>
METHODS: <br/><br>
Human CD34(+) cells from cord blood were cultured in vitro for eleven or eight days in the presence or absence of Angptls. The reconstitution capacity of expanded cells was subsequently measured in vivo by transplantation into NOD-SCID or NSG mice, and compared to that of uncultured cells. <br/><br>
<br/><br>
RESULTS: <br/><br>
We report here that Angptl4 functions to maintain SRC-activity of CD34(+) CB-derived cells ex vivo as assayed in NOD-SCID and NSG mice. However, all Angptls tested, including Angptl1, 4, and 5, were associated with variation between experiments. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
Our findings indicate that Angptl4 and Angptl5 can lead to increased engraftment capacity of SRCs, but more frequently these factors are associated with maintenance of SRC-activity during ex vivo culture. Thus, Angptl-mediated expansion of SRCs ex vivo is associated with more inter-experimental variation than previously thought. We conclude that Angptls would be useful in instances where there is a need to maintain HSCs ex vivo, such as during transduction for gene therapy applications.},
  author       = {Blank Savukinas, Ulrika and Ehrnström, Birgitta and Heinz, Niels and Nilsson, Eva C and Brun, Ann and Baum, Christopher and Schiedlmeier, Bernhard and Karlsson, Stefan},
  issn         = {1600-0609},
  language     = {eng},
  number       = {3},
  pages        = {198--205},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Haematology},
  title        = {Angptl4 maintains in vivo repopulation capacity of CD34(+) human cord blood cells.},
  url          = {http://dx.doi.org/10.1111/j.1600-0609.2012.01812.x},
  volume       = {89},
  year         = {2012},
}