Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Foßelteder, J; Brauchart, T; Schlacher, A; Sconocchia, T; Özkaya, E; Auinger, L; Schlenke, P; Sill, H; Zebisch, A; Reinisch, A.
Engineered cytokine-expressing MSCs support ex vivo culture of human HSPCs and AML cells.
Exp Hematol. 2025; 104790
Doi: 10.1016/j.exphem.2025.104790
PubMed
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- Führende Autor*innen der Med Uni Graz
- Foßelteder Johannes
- Reinisch Andreas
- Co-Autor*innen der Med Uni Graz
- Brauchart Thomas
- Özkaya Erdem
- Schlenke Peter
- Sconocchia Tommaso
- Sill Heinz
- Zebisch Armin
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- Abstract:
- CD34+ human hematopoietic stem and progenitor cells (HSPCs) and primary patient-derived leukemia cells are important tools for basic and translational research. Their limited availability demands additional expansion ex vivo in many cases. The use of either cytokine cocktails or co-cultures with mesenchymal stromal cells (MSCs) has advanced cell expansion but combinations of both have not been addressed extensively so far. Here, we present a novel approach to generate human cytokine-expressing MSCs (ceMSCs) via genetic engineering. Co-culture with ceMSCs and their culture supernatant led to an efficient expansion and maintenance of functional CD34+CD45RA-CD90+CD201+CD49c+ HSCs ex vivo. Similarly, ceMSCs and their culture supernatant support the growth of cytokine-dependent leukemic cell lines in vitro, and improved the survival, maintenance, and expansion of patient-derived acute myeloid leukemia (AML) cells, a cell population very challenging to be cultured ex vivo. ceMSCs even surpass the support provided by wild-type MSCs or external cytokines alone. Therefore, ceMSCs offer a cost-effective, straightforward alternative to traditional cytokine supplementation, enhancing the feasibility of ex vivo studies on healthy and leukemic stem and progenitor cells, including therapeutic drug testing and mechanistic investigations.