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

Ciprian Tomuleasa, Sonia Selicean, Grigore Gafencu, Bobe Petrushev, Laura Pop, Cristian Berce, Anca Jurj, Adrian Trifa, Ana Maria Rosu, Sergiu Pasca, Lorand Magdo, Mihnea Zdrenghea, Delia Dima, Alina Tanase, Ioana Frinc, Anca Bojan, Ioana Berindan-Neagoe, Gabriel Ghiaur, Stefan O. Ciurea

Research output: Contribution to journalArticle

Abstract

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.

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Keywords

  • Anti-fibrotic drug screening
  • Fibroblasts
  • Primary myelofibrosis

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Tomuleasa, C., Selicean, S., Gafencu, G., Petrushev, B., Pop, L., Berce, C., ... Ciurea, S. O. (Accepted/In press). Fibroblast dynamics as an in vitro screening platform for anti-fibrotic drugs in primary myelofibrosis. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.25902