There are many promising treatments emerging from some very elegant pre-clinical studies, which range from: stem cell therapies to prevent the deposition of scar tissue; the use of pharmaceutical agents that reduce scarring through TGF[beta] inhibition, modulate collagen synthesis and reduce
myofibroblast formation; and the use of viral and nanoparticle gene therapies to enhance stromal remodelling in the cornea.
Fibrosis occurs when a wound or injury causes a certain type of healing cell, called fibroblast, to morph into a different type of cell called
myofibroblast in order to heal the wound.
The literature on biology of reactive stroma (the
myofibroblast or tumor-activated fibroblasts in PCa) far outweighs what we have been able to identify in the pathology literature.
In particular the role of TGFB has been highlighted in tissue fibrosis - reported to contribute to around 40% of deaths worldwide annually- where it is recognised as a critical mediator of fibroblast to
myofibroblast differentiation and aberrant matrix deposition.
The aim of this study was to elucidate whether and how YAP plays a role in
myofibroblast differentiation in the context of Ang II and the pathophysiology of DCM.
Primary cells at passages 3-4 were used for
myofibroblast activation and ECM production assays.
The team found that adalimumab (at a dose of 40mg formulated in 0.4ml) reduces expression of the fibrotic markers, -smooth muscle actin (-SMA) and type I procollagen, at 2 weeks post-injection, suggesting this drug could be used to stop the growth of disease-causing
myofibroblast cells.
Using a mouse model, the team identified a specific cell called a subepithelial
myofibroblast as an essential source of both Wnts and RSPO3.
This Small Business Innovation Research (SBIR) funding will support Phelix's continued research of Calpain therapeutics to inhibit
myofibroblast generation in fibrosis for the treatment of fibrotic diseases such as IPF and NASH.
Fibrogenesis is initiated by
myofibroblast activation and proliferation because activated
myofibroblasts are the major source of ECM in the injured liver (2,3).
In this study there was no change in the morphology of LX-2 cells in both normal and treatment groups because it was already an active form of HSC,
myofibroblast like phenotypes.
Since the increased presence of [Gr-1.sup.+] myeloid cells had a marked effect on the expression of ECM proteins such as procollagen 3 and fibronectin 1 and the profibrotic mediator, TGF-[beta], we hypothesized that these cells might inhibit
myofibroblast ECM generation.
