Adipose tissue-derived stromal cell conditioned medium can inhibit the fibrotic behavior of fibroblasts induced by the extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF), according to a new study published in Frontiers in Pharmacology

The antifibrotic effects of adipose tissue-derived stromal cell conditioned medium had already been demonstrated in animal models but had not been tested in human tissues.

“Our findings open up new avenues for [adipose tissue-derived stromal cell conditioned medium] to be explored as [a] treatment for IPF,” the researchers wrote.


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In the present study, a team of researchers led by Janette K. Burgess from the University Medical Center Groningen
in the Netherlands investigated the structural integrity of collagen in fibrotic lung tissue, its interactions with fibroblasts, and the effects of adipose tissue-derived stromal cell conditioned medium treatment.

Using fibrotic and nonfibrotic lung tissues, the team first showed that there was more denatured collagen in IPF tissue than in control tissue in both decellularized and native tissues.

When they recellularized the tissues with fibroblasts, the researchers found that the level of denatured collagen was equalized between both types of tissue. However, the total ECM was still higher in IPF matrices than in control tissues. 

Treatment with adipose tissue-derived stromal cell conditioned medium led to less ECM deposition. However, it did not change the level of denatured collagen.

“These findings further confirm…that the use of [adipose tissue-derived stromal cell conditioned medium] may be a promising approach to stop fibrotic ECM from directing profibrotic behavior in fibroblasts in IPF,” the researchers concluded.

Adipose tissue-derived stromal cell conditioned medium contains various molecules that are important for tissue regeneration, apoptosis, host cell proliferation, and angiogenesis. The use of this medium instead of adipose tissue-derived stromal cells themselves prevents the potentially harmful effects of these cells, which could react detrimentally in a profibrotic environment.

The use of decellularized matrices allows researchers to study the influence of the ECM on cellular behavior and the impact of soluble factors on these cell-matrix interactions. Recellularizing these matrices provides information about how these cells respond to matrix remodeling.

Reference

Vasse GF, Van Os L, De Jager M, et al. Adipose stromal cell-secretome counteracts profibrotic signals from IPF lung matrices. Front Pharmacol. Published online July 28, 2021. doi:10.3389/fphar.2021.669037