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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; 147:104790
Doi: 10.1016/j.exphem.2025.104790
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
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Foßelteder Johannes
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Reinisch Andreas
- Co-authors Med Uni Graz
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Brauchart Thomas
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Özkaya Erdem
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Schlenke Peter
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Sconocchia Tommaso
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Sill Heinz
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Zebisch Armin
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- Abstract:
- CD34+ human hematopoietic stem and progenitor cells 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 cocultures with mesenchymal stromal cells (MSCs) has advanced cell expansion but combinations of both have not been addressed extensively so far. Here, we presented a novel approach to generating human cytokine-expressing MSCs (ceMSCs) using genetic engineering. Coculture with ceMSCs and their culture supernatant led to an efficient expansion and maintenance of functional CD34+CD45RA-CD90+CD201+CD49c+ hematopoietic stem cells ex vivo. Similarly, ceMSCs and their culture supernatant support the growth of cytokine-dependent leukemic cell lines in vitro and improve the survival, maintenance, and expansion of patient-derived acute myeloid leukemia 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.
- Find related publications in this database (using NLM MeSH Indexing)
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Humans - administration & dosage
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Mesenchymal Stem Cells - metabolism, cytology
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Cytokines - genetics, biosynthesis
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Leukemia, Myeloid, Acute - pathology, metabolism, genetics
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Hematopoietic Stem Cells - metabolism, cytology, pathology
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Coculture Techniques - administration & dosage
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Genetic Engineering - administration & dosage
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Cell Line, Tumor - administration & dosage
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Cell Culture Techniques - administration & dosage