Fibroblast dynamics as an in vitro screening platform for anti-fibrotic drugs in primary myelofibrosis

J Cell Physiol. 2018 Jan;233(1):422-433. doi: 10.1002/jcp.25902. Epub 2017 May 23.


Although the cause for bone marrow fibrosis in patients with myelofibrosis remains controversial, it has been hypothesized that it is caused by extensive fibroblast proliferation under the influence of cytokines generated by the malignant megakaryocytes. Moreover, there is no known drug therapy which could reverse the process. We studied the fibroblasts in a novel system using the hanging drop method, evaluated whether the fibroblasts obtain from patients are part of the malignant clone of not and, using this system, we screen a large library of FDA-approved drugs to identify potential drugs candidates that might be useful in the treatment of this disease, specifically which would inhibit fibroblast proliferation and the development of bone marrow fibrosis. We have found that the BM fibroblasts are not part of the malignant clone, as previously suspected and two immunosuppressive medications-cyclosporine and mycophenolate mophetil, as most potent suppressors of the fibroblast collagen production thus potentially inhibitors of bone marrow fibrosis production in myelofibrosis.

Keywords: anti-fibrotic drug screening; fibroblasts; primary myelofibrosis.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects*
  • Collagen / metabolism*
  • Cyclosporine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery / instrumentation*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis
  • Gene Expression Regulation
  • High-Throughput Screening Assays*
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Kinetics
  • Mutation
  • Mycophenolic Acid / pharmacology*
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / metabolism
  • Primary Myelofibrosis / pathology
  • Transforming Growth Factor beta / pharmacology


  • Transforming Growth Factor beta
  • Cyclosporine
  • Collagen
  • JAK2 protein, human
  • Janus Kinase 2
  • Mycophenolic Acid