Adipose stem cell secretome as a potential treatment for urethral fibrosis

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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Barasa, Povilas (Vilnius University, Life Sciences Center, Institute of Biochemistry )


Urethral fibrosis affects 1 out of 1000 individuals within their lifetime, most of those affected being male. It shares the hallmarks of other types of fibrosis (e.g., liver or heart), namely, the activation of myofibroblasts, overabundance of collagen and the spread of scarring from the initial focus to the surrounding tissue, leading to organ failure. It can be caused by trauma, infection and chronic inflammation; in the case of urethral fibrosis, the cause is occasionally iatrogenic. Currently, the most effective treatment of fibrosis is organ or tissue transplantation (if possible); there are several pharmaceuticals used as well, however, the options are limited and new ways of treating fibrosis need to be investigated. The secretome of stem cells has been explored for treating various diseases; for example, it has shown promise in the case of treating idiopathic pulmonary fibrosis. Nevertheless, both the causes of fibrosis and the molecular mechanisms that could be affected to prevent or treat this illness have not yet been elucidated. Thus we decided to investigate the effect the stem cell secretome has on myofibroblasts, and whether this could reveal new ways of fibrosis treatment.

Primary human myofibroblasts (HMF) were isolated from scarred urethral tissue and confirmed to present the α-smooth muscle actin (αSMA) myofibroblast marker. Human adipose stem cells (HASC) were isolated from adipose tissue and shown to be CD44 and CD90 positive. Their differentiation multipotential was also confirmed. WPMY-1 prostate cancer stromal myofibroblasts (ATCC) was chosen as a control cell line. To better recapture the fibrotic environment found in the affected tissues, the myofibroblast cells were cultivated on PDMS coated with fibronectin. The effect of the HASC conditioned medium (HASC-CM) was compared to the effect of treatment using a common antifibrotic drug at a therapeutic concentration. Treatment effects were analyzed by performing Western blot for αSMA and latent TGFβ, another player in fibrosis development. Moreover, the gene expression levels of fibrosis-related and TGFβ signalling pathway genes were quantified.

The myofibroblasts cultivated on fibronectin-coated PDMS exhibited significant differences in fibrosis-related gene expression levels compared to cells cultivated on tissue culture plate surface, confirming the importance of tuning the cultivation surface to the natural cell environment. Both the HMF and WPMY cells showed clear differences after treatment with either HASC-CM or antifibrotic drug, with the increase of latent TGFβ (both treatments) and changes in αSMA amount (decreased in the drug group, increased in CM group). The gene expression changes after treatment were also evident: cells expressed more Mmp1 (collagenase I, an anti-fibrotic marker) and less Ctgf (pro-fibrotic marker) after treatment with CM. Lastly, as treatment with CM did not reduce Tgfb expression, our findings point the anti-fibrotic effect may be elicited through reduction of Rock1 and Rock2 expression.

We summarize that the adipose stem cell secretome reduces the amount of fibrotic markers in myofibroblast culture, although through different mechanisms than conventional anti-fibrotic drugs.

This project has received funding from European Regional Development Fund (project No. 01.2.2-LMT-K-718-03-0087) under grant agreement with the Research Council of Lithuania (LMTLT).


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