Adipose Stromal Cell-Secretome Counteracts Profibrotic Signals From IPF Lung Matrices.

Autor:	Vasse GF; University of Groningen, University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, W.J. Kolff Institute for Biomedical Engineering and Materials Science, Groningen, Netherlands.; University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands., Van Os L; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands., De Jager M; University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, Groningen, Netherlands., Jonker MR; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands., Borghuis T; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands., Van Den Toorn LT; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands., Jellema P; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands., White ES; Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI, United States., Van Rijn P; University of Groningen, University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, W.J. Kolff Institute for Biomedical Engineering and Materials Science, Groningen, Netherlands., Harmsen MC; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands., Heijink IH; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, Netherlands., Melgert BN; University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands., Burgess JK; University of Groningen, University Medical Center Groningen, W.J. Kolff Institute for Biomedical Engineering and Materials Science, Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2021 Jul 28; Vol. 12, pp. 669037. Date of Electronic Publication: 2021 Jul 28 (Print Publication: 2021).
DOI:	10.3389/fphar.2021.669037
Abstrakt:	Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by excess deposition and altered structure of extracellular matrix (ECM) in the lungs. The fibrotic ECM is paramount in directing resident cells toward a profibrotic phenotype. Collagens, an important part of the fibrotic ECM, have been shown to be structurally different in IPF. To further understand the disease to develop better treatments, the signals from the ECM that drive fibrosis need to be identified. Adipose tissue-derived stromal cell conditioned medium (ASC-CM) has demonstrated antifibrotic effects in animal studies but has not been tested in human samples yet. In this study, the collagen structural integrity in (fibrotic) lung tissue, its interactions with fibroblasts and effects of ASC-CM treatment hereon were studied. Methods: Native and decellularized lung tissue from patients with IPF and controls were stained for denatured collagen using a collagen hybridizing peptide. Primary lung fibroblasts were seeded into decellularized matrices from IPF and control subjects and cultured for 7 days in the presence or absence of ASC-CM. Reseeded matrices were fixed, stained and analyzed for total tissue deposition and specific protein expression. Results: In both native and decellularized lung tissue, more denatured collagen was observed in IPF tissue compared to control tissue. Upon recellularization with fibroblasts, the presence of denatured collagen was equalized in IPF and control matrices, whereas total ECM was higher in IPF matrices than in the control. Treatment with ASC-CM resulted in less ECM deposition, but did not alter the levels of denatured collagen. Discussion: Our data showed that ASC-CM can inhibit fibrotic ECM-induced profibrotic behavior of fibroblasts. This process was independent of collagen structural integrity. Our findings open up new avenues for ASC-CM to be explored as treatment for IPF. Competing Interests: PR is co-founder, scientific advisor, and shareholder of BiomACS BV, a biomedical-oriented screening company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Vasse, Van Os, De Jager, Jonker, Borghuis, Van Den Toorn, Jellema, White, Van Rijn, Harmsen, Heijink, Melgert and Burgess.)
Databáze:	MEDLINE
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