Maintenance of mouse hematopoietic stem cells ex vivo by reprogramming cellular metabolism

Xia Liu, Hong Zheng, Wen Mei Yu, Todd M. Cooper, Kevin D. Bunting, Cheng Kui Qu

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The difficulty in maintaining the reconstituting capabilities of hematopoietic stem cells (HSCs) in culture outside of the bone marrow microenvironment has severely limited their utilization for clinical therapy. This hurdle is largely due to the differentiation of long-term stem cells. Emerging evidence suggests that energy metabolism plays an important role in coordinating HSC self-renewal and differentiation. Here, we show that treatment with alexidine dihydrochloride, an antibiotic and a selective inhibitor of the mitochondrial phosphatase Ptpmt1, which is crucial for the differentiation of HSCs, reprogrammed cellular metabolism from mitochondrial aerobic metabolism to glycolysis, resulting in a remarkable preservation of long-term HSCs ex vivo in part through hyperactivation of adenosine 5′-monophosphate-activated protein kinase (AMPK). In addition, inhibition of mitochondrial metabolism and activation of AMPK by metformin, a diabetes drug, also decreased differentiation and helped maintain stem cells in culture. Thus, manipulating metabolic pathways represents an effective new strategy for ex vivo maintenance of HSCs.

Original languageEnglish
Pages (from-to)1562-1565
Number of pages4
JournalBlood
Volume125
Issue number10
DOIs
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 by The American Society of Hematology.

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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