IL3 Has a Detrimental Effect on Hematopoietic Stem Cell Self-Renewal in Transplantation Settings

The ex vivo expansion and maintenance of long-term hematopoietic stem cells (LT-HSC) is crucial for stem cell-based gene therapy. A combination of stem cell factor (SCF), thrombopoietin (TPO), FLT3 ligand (FLT3) and interleukin 3 (IL3) cytokines has been commonly used in clinical settings for the ex...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-11, Vol.23 (21), p.12736
Main Authors: Tajer, Parisa, Canté-Barrett, Kirsten, Naber, Brigitta A. E., Vloemans, Sandra A., van Eggermond, Marja C. J. A., van der Hoorn, Marie-Louise, Pike-Overzet, Karin, Staal, Frank J. T.
Format: Article
Language:English
Subjects:
Bone marrow
CD34 antigen
Cell cycle
Cell division
Cell self-renewal
Cytokines
Flow cytometry
FLT3L protein
Gene therapy
Granulocytes
Hematopoietic stem cells
Interleukin 3
Ligands
Spleen
Stem cell factor
Stem cell transplantation
Stem cells
Thrombopoietin
Thymus gland
Transplantation
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Summary:The ex vivo expansion and maintenance of long-term hematopoietic stem cells (LT-HSC) is crucial for stem cell-based gene therapy. A combination of stem cell factor (SCF), thrombopoietin (TPO), FLT3 ligand (FLT3) and interleukin 3 (IL3) cytokines has been commonly used in clinical settings for the expansion of CD34+ from different sources, prior to transplantation. To assess the effect of IL3 on repopulating capacity of cultured CD34+ cells, we employed the commonly used combination of STF, TPO and FILT3 with or without IL3. Expanded cells were transplanted into NSG mice, followed by secondary transplantation. Overall, this study shows that IL3 leads to lower human cell engraftment and repopulating capacity in NSG mice, suggesting a negative effect of IL3 on HSC self-renewal. We, therefore, recommend omitting IL3 from HSC-based gene therapy protocols.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms232112736