Klin Padiatr 2017; 229(03): 182-195
DOI: 10.1055/s-0037-1602199
Top 2 Stem cell research and transplantation
Georg Thieme Verlag KG Stuttgart · New York

Combination of ex vivo expansion with apoptosis inhibition in donor hematopoietic stem cells

PMA Zehnle
1   Division of Pediatric Hematology and Oncology, Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg
,
M Kollek
1   Division of Pediatric Hematology and Oncology, Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg
,
F Murad
2   Division of Membrane Biophysics, University of Tübingen, Tübingen
,
N Fischer
1   Division of Pediatric Hematology and Oncology, Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg
,
M Kunze
3   Department of Obstetrics and Gynecology, University Medical Center Freiburg, Freiburg, Germany
,
A Garcia-Saez
2   Division of Membrane Biophysics, University of Tübingen, Tübingen
,
M Erlacher
1   Division of Pediatric Hematology and Oncology, Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg
› Author Affiliations
Further Information

Publication History

Publication Date:
30 May 2017 (online)

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Introduction:

Transplantation of low numbers of donor hematopoietic stem cells is associated with the risk of severe complications such as graft failure or delayed engraftment. We have shown earlier that inhibition of apoptosis in donor cells results in the transplantation of fitter stem cells and in improved engraftment. Here, we aim at further increasing the numbers of donor stem cells by combining ex vivo stem cell expansion with apoptosis inhibition prior to and during transplantation.

Methods:

We used StemRegenin 1 for the expansion of hematopoietic stem cells in culture. To inhibit apoptosis during the expansion period several approaches were tested, i.e. caspase inhibition, lentiviral Bcl-XL overexpression or protein transduction of Bcl-XL coupled to a cell-penetrating peptide. Proliferation, differentiation and cell death were determined by flow cytometry.

Results:

Stem cell expansion is associated with increased apoptosis in vitro and this cell death can be partly inhibited by anti-apoptotic treatment.

Conclusion:

We will investigate whether the combination of stem cell expansion with apoptosis inhibition improves the outcome of stem cell transplantation in xenograft models.