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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

Ciclopirox Ethanolamine Preserves the Immature State of Human HSCs by Mediating Intracellular Iron Content

Author

  • Mehrnaz Safaee Talkhoncheh
  • Aurélie Baudet
  • Fredrik Ek
  • Agatheeswaran Subramaniam
  • Yun-Ruei Kao
  • Natsumi Miharada
  • Christine Karlsson
  • Leal Oburoglu
  • Anna Rydström
  • Kristijonas Žemaitis
  • Abdul Ghani Alattar
  • Justyna Rak
  • Kristian Pietras
  • Roger Olsson
  • Britta Will
  • Jonas Larsson
Show all

Summary, in English

Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. To elucidate regulatory mechanisms governing the maintenance and propagation of human HSCs ex vivo, we screened libraries of annotated small molecules in human cord blood (CB) cells using an optimized assay for detection of functional HSCs during culture. We found that the antifungal agent ciclopirox ethanolamine (CPX) selectively supported immature CD34+CD90+ cells during culture and enhanced their long-term in vivo repopulation capacity. Purified HSCs treated with CPX showed a reduced cell division rate and an enrichment of HSC- specific gene expression patterns. Mechanistically, we found that the HSC stimulating effect of CPX was directly mediated by chelation of the intracellular iron pool, which in turn affected iron-dependent proteins and enzymes mediating cellular metabolism and respiration. Our findings unveil a significant impact of iron homeostasis in regulation of human HSCs, with important implications for both basic HSC biology and clinical hematology.

Department/s

  • LUCC: Lund University Cancer Centre
  • Experimental oncology
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • LU Profile Area: Light and Materials
  • LTH Profile Area: Nanoscience and Semiconductor Technology
  • NanoLund: Centre for Nanoscience
  • Chemical Biology and Therapeutics
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease
  • Hematogenomics
  • Hematopoietic Stem Cell Development
  • Transfusion Medicine
  • Stem Cells to Red Blood Cells
  • Division of Molecular Medicine and Gene Therapy
  • Clinical Physiology and Nuclear Medicine, Malmö

Publishing year

2023-07-24

Language

English

Publication/Series

Blood Advances

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Medical Biotechnology
  • Cell and Molecular Biology

Status

Epub

Research group

  • Experimental oncology
  • Chemical Biology and Therapeutics
  • Hematogenomics
  • Hematopoietic Stem Cell Development
  • Transfusion Medicine
  • Stem Cells to Red Blood Cells
  • Clinical Physiology, Malmö

ISBN/ISSN/Other

  • ISSN: 2473-9529