Effects of adjuvant chemotherapy on bone marrow mesenchymal stem cells of colorectal cancer patients

Cancer Lett. 2008 May 18;263(2):197-203. doi: 10.1016/j.canlet.2008.01.011. Epub 2008 Mar 4.

Abstract

Background: Chemotherapy damages the bone marrow and that is one of the most important problems in the treatment of malignancies, particularly colorectal cancer. The aim of the present study was to assess the effects of surgical adjuvant chemotherapy for CRC patients on human MSCs using an in vitro culture system.

Methods: The bone marrows of 43 CRC patients were harvested for separation and culture of MSC at pre- and post-chemotherapy. The number of colonies forming unit-fibroblast (CFU-F) was counted. The adhesive function of MSC was assayed and the growth of colony-forming unit-mixed hematopoietic cell (CFU-Mix) on the MSC layer was observed. The concentration of IL-6, SCF and FLT-T3 proteins in the MSC culture supernatant were also detected by ELISA assay.

Results: In the CRC patients with chemotherapy, we have demonstrated that the CFU-F exhibit significantly decreased. We also showed that the adhesive rate of bone marrow mesenchymal stem cell (BMSC) was significantly decreased. The growth of CFU-Mix on the MSC layer was inhibited. Most importantly, decreased CFU-F and the adhesive rate of BMSC were correlated significantly with decreased interleukins and stem-cell factor (IL-6, SCF and FLT-3L) expressions in the CRC patients after chemotherapy.

Conclusion: Our results suggest that MSCs of CRC patients can be damaged by chemotherapy. Our data also indicates that the decreased expression of haematogenesis factors may play an important role in the pathogenesis. In the future, the MSC refused may have a potential clinical application in chemotherapeutically treated patients.

MeSH terms

  • Aged
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / pathology
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape
  • Cells, Cultured
  • Chemotherapy, Adjuvant / adverse effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / surgery
  • Cytokines / analysis
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / pathology
  • Middle Aged
  • Tumor Stem Cell Assay

Substances

  • Cytokines