Back to Search
Start Over
Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis.
- Source :
-
PloS one [PLoS One] 2017 Jan 30; Vol. 12 (1), pp. e0166014. Date of Electronic Publication: 2017 Jan 30 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo. TGFβ production by malignant megakaryocytes plays a definitive role promoting myelofibrosis in MPNs. However, TGFβ was equally expressed by MSCs derived from MPLWT and MPLW515L expressing mice and the addition of neutralizing anti-TGFβ antibody only partially reduced collagen secretion in vitro. Interestingly, profibrotic MSCs displayed increased levels of pSmad3 and pSTAT3 suggesting that inflammatory mediators cooperating with the TGFβ-receptor signaling may maintain the aberrant phenotype ex vivo. FGFb is a known suppressor of TGFβ signaling. Reduced collagen deposition by FGFb-treated MSCs derived from MPLW515L mice suggests that the activating pathway is vulnerable to this suppressive mediator. Therefore, our findings have implications for the future investigation of therapies to reverse fibrosis in MPNs.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Bone Marrow Cells metabolism
Cell Proliferation
Collagen biosynthesis
Disease Models, Animal
Humans
Mesenchymal Stem Cell Transplantation
Mice, Inbred C57BL
Phenotype
Receptors, Thrombopoietin genetics
Signal Transduction
Transduction, Genetic
Transforming Growth Factor beta biosynthesis
Cellular Reprogramming
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells metabolism
Primary Myelofibrosis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28135282
- Full Text :
- https://doi.org/10.1371/journal.pone.0166014