Mesenchymal stem cells preserve their stem cell traits after exposure to antimetabolite chemotherapy

Ramon Lopez Perez, Franziska Münz, Denise Vidoni, Alexander Rühle, Thuy Trinh, Sonevisay Sisombath, Bingwen Zou, Patrick Wuchter, Jürgen Debus, Anca Ligia Grosu, Rainer Saffrich, Peter E. Huber, Nils H. Nicolay

Research output: Contribution to journalArticle

Abstract

Background: Mesenchymal stem cells (MSCs) participate in the regeneration of tissue lesions induced by antimetabolite chemotherapy; however, the influence of this class of anti-cancer compounds on the stem cells remains largely unknown. Methods: The survival of MSCs after exposure to 5-fluorouracil (5-FU) and gemcitabine was measured by viability and clonogenic assays. MSC morphology, surface marker expression, adhesion potential, cellular velocity and differentiation potential were determined after antimetabolite treatment. Cell cycle distribution and apoptosis were assessed using flow cytometry, and senescence induction was evaluated by beta-galactosidase staining. Gene expression arrays were used to analyze the expression of enzymes involved in DNA metabolism and multidrug resistance. Results: Here, we show that human primary bone marrow MSCs are relatively resistant to treatment with the widely used antimetabolite drugs 5-FU and gemcitabine. The stem cells were able to largely retain their functional abilities and defining stem cell traits after antimetabolite exposure. MSCs surface markers were found stably expressed, and the characteristic multi-lineage differentiation potential was maintained irrespective of 5-FU or gemcitabine treatment. High expression levels of enzymes involved in DNA metabolism and multidrug resistance transporters may contribute to the resistance to antimetabolite chemotherapy. Discussion: The observed resistance and functional integrity may form the basis for further investigations of MSCs as a potential therapy for antimetabolite-induced tissue damage.

Original languageEnglish (US)
Article number101536
JournalStem Cell Research
Volume40
DOIs
StatePublished - Oct 2019

Fingerprint

Antimetabolites
gemcitabine
Mesenchymal Stromal Cells
Stem Cells
Drug Therapy
Fluorouracil
Multiple Drug Resistance
DNA
Enzymes
Therapeutics
beta-Galactosidase
Regeneration
Cell Cycle
Flow Cytometry
Bone Marrow
Apoptosis
Staining and Labeling
Gene Expression
Pharmaceutical Preparations
Neoplasms

Keywords

  • Antineoplastic agents
  • Fluorouracil
  • Gemcitabine
  • Mesenchymal stem cells (MSCs)
  • Mesenchymal stromal cells (MSCs)
  • Neoplasms
  • Stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Lopez Perez, R., Münz, F., Vidoni, D., Rühle, A., Trinh, T., Sisombath, S., ... Nicolay, N. H. (2019). Mesenchymal stem cells preserve their stem cell traits after exposure to antimetabolite chemotherapy. Stem Cell Research, 40, [101536]. https://doi.org/10.1016/j.scr.2019.101536

Mesenchymal stem cells preserve their stem cell traits after exposure to antimetabolite chemotherapy. / Lopez Perez, Ramon; Münz, Franziska; Vidoni, Denise; Rühle, Alexander; Trinh, Thuy; Sisombath, Sonevisay; Zou, Bingwen; Wuchter, Patrick; Debus, Jürgen; Grosu, Anca Ligia; Saffrich, Rainer; Huber, Peter E.; Nicolay, Nils H.

In: Stem Cell Research, Vol. 40, 101536, 10.2019.

Research output: Contribution to journalArticle

Lopez Perez, R, Münz, F, Vidoni, D, Rühle, A, Trinh, T, Sisombath, S, Zou, B, Wuchter, P, Debus, J, Grosu, AL, Saffrich, R, Huber, PE & Nicolay, NH 2019, 'Mesenchymal stem cells preserve their stem cell traits after exposure to antimetabolite chemotherapy', Stem Cell Research, vol. 40, 101536. https://doi.org/10.1016/j.scr.2019.101536
Lopez Perez, Ramon ; Münz, Franziska ; Vidoni, Denise ; Rühle, Alexander ; Trinh, Thuy ; Sisombath, Sonevisay ; Zou, Bingwen ; Wuchter, Patrick ; Debus, Jürgen ; Grosu, Anca Ligia ; Saffrich, Rainer ; Huber, Peter E. ; Nicolay, Nils H. / Mesenchymal stem cells preserve their stem cell traits after exposure to antimetabolite chemotherapy. In: Stem Cell Research. 2019 ; Vol. 40.
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AU - Sisombath, Sonevisay

AU - Zou, Bingwen

AU - Wuchter, Patrick

AU - Debus, Jürgen

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