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Article

Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro

1
Department of Pulmonary Medicine, University Hospital Bern, 3008 Bern, Switzerland
2
Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland
3
Graduate School, University of Bern, 3008 Bern, Switzerland
4
Interfaculty Bioinformatics Unit, University of Bern, 3008 Bern, Switzerland
5
Department of Gynecology and Obstetrics, Cantonal Hospital Fribourg, 1702 Fribourg, Switzerland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(2), 958; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020958
Received: 31 December 2020 / Revised: 15 January 2021 / Accepted: 17 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery)
Macrophages play essential role in repair, regeneration and tissue remodeling. Role of macrophages in progression of lung fibrosis is established. Secretome of Induced pluripotent stem cells (iPSC-CM) has shown to reduce lung fibrosis and regulate macrophage phenotype, however exact mechanism is not known. Using advanced bioinformatics analysis by gene network analysis in this study we identified two components AAP and ELAVL-1 present in the iPSC-CM playing important role in regulation of macrophage phenotype. In this invitro study we confirmed experimentally that AAP and ELAVL1 play essential role by changing the profibrotic phenotype of the macrophages to pro resolution macrophages. We demonstrate reduction in gene expression and cytokine secretion of profibrotic macrophages after iPSC-CM treatment. Our study confirms antifibrotic and regenerative potential of iPSC-CM.
Induced pluripotent stem cell secretome (iPSC-CM) mitigate organ injury and help in repair. Macrophages play a critical role in tissue repair and regeneration and can be directed to promote tissue repair by iPSC-CM, although the exact mechanisms are not known. In the current investigative study, we evaluated the possible mechanism by which iPSC-CM regulates the phenotype and secretory pattern of macrophages in vitro. Macrophages were obtained from human peripheral blood mononuclear cells and differentiated to various subpopulations and treated with either iPSC-CM or control media in vitro. Macrophage phenotype was assessed by flow cytometry, gene expression changes by qRT PCR and secretory pattern by multiplex protein analysis. The protein and gene interaction network revealed the involvement of Amyloid precursor protein (APP) and ELAV-like protein 1 (ELAVL-1) both present in the iPSC-CM to play an important role in regulating the macrophage phenotype and their secretory pattern. This exploratory study reveals, in part, the possible mechanism and identifies two potential targets by which iPSC-CM regulate macrophages and help in repair and regeneration. View Full-Text
Keywords: lung fibrosis; macrophages; induced pluripotent stem cells; stem cells secretome; lung repair and regeneration lung fibrosis; macrophages; induced pluripotent stem cells; stem cells secretome; lung repair and regeneration
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MDPI and ACS Style

Tamò, L.; Fytianos, K.; Caldana, F.; Simillion, C.; Feki, A.; Nita, I.; Heller, M.; Geiser, T.; Gazdhar, A. Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro. Int. J. Mol. Sci. 2021, 22, 958. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020958

AMA Style

Tamò L, Fytianos K, Caldana F, Simillion C, Feki A, Nita I, Heller M, Geiser T, Gazdhar A. Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro. International Journal of Molecular Sciences. 2021; 22(2):958. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020958

Chicago/Turabian Style

Tamò, Luca, Kleanthis Fytianos, Fabienne Caldana, Cedric Simillion, Anis Feki, Izabela Nita, Manfred Heller, Thomas Geiser, and Amiq Gazdhar. 2021. "Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro" International Journal of Molecular Sciences 22, no. 2: 958. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020958

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