TNF-α Preconditioning Promotes a Proangiogenic Phenotype in hiPSC-Derived Vascular Smooth Muscle Cells.

Autor: Sasson DC; Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, 330 Cedar Street, Boardman Bldg, 3rd Floor, New Haven, CT 06510 USA., Islam S; Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, 330 Cedar Street, Boardman Bldg, 3rd Floor, New Haven, CT 06510 USA., Duan K; Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, 330 Cedar Street, Boardman Bldg, 3rd Floor, New Haven, CT 06510 USA., Dash BC; Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, 330 Cedar Street, Boardman Bldg, 3rd Floor, New Haven, CT 06510 USA.; Department of Biomedical Engineering, Yale School of Engineering & Applied Science, New Haven, CT USA., Hsia HC; Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, 330 Cedar Street, Boardman Bldg, 3rd Floor, New Haven, CT 06510 USA.; Department of Biomedical Engineering, Yale School of Engineering & Applied Science, New Haven, CT USA.
Jazyk: angličtina
Zdroj: Cellular and molecular bioengineering [Cell Mol Bioeng] 2023 Apr 08; Vol. 16 (3), pp. 231-240. Date of Electronic Publication: 2023 Apr 08 (Print Publication: 2023).
DOI: 10.1007/s12195-023-00764-0
Abstrakt: Introduction: hiPSC-VSMCs have been suggested as therapeutic agents for wound healing and revascularization through the secretion of proangiogenic factors. However, methods of increasing cell paracrine secretion and survivability have thus far yielded inconsistent results. This study investigates the effect of pre-conditioning of hiPSC-VSMCs with TNF-α and their integration into 3D collagen scaffolds on cellular viability and secretome.
Methods: hiPSC-VSMCs were dual-plated in a 2D environment. TNF-α was introduced to one plate. Following incubation, cells from each plate were divided and added to type-I collagen scaffolds. TNF-α was introduced to two sets of scaffolds, one from each 2D plate. Following incubation, scaffolds were harvested for their media, tested for cell survivability, cytotoxicity, and imaged. Intra-media VEGF and bFGF levels were evaluated using ELISA testing.
Results: hiPSC-VSMCs exposed to TNF-α during collagen scaffold proliferation and preconditioning showed an increase in cell viability and less cytotoxicity compared to non-exposed cells and solely-preconditioned cells. Significant increases in bFGF expression were found in pre-conditioned cell groups with further increases found in cells subsequently exposed during intra-scaffold conditioning. A significant increase in VEGF expression was found in cell groups exposed during both pre-conditioning and intra-scaffold conditioning. Fibroblasts treated with any conditioned media demonstrated increased migration potential.
Conclusions: Conditioning hiPSC-VSMCs embedded in scaffolds with TNF-α improves cellular viability and increases the secretion of paracrine factors necessary for wound healing mechanisms such as migration.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00764-0.
Competing Interests: Conflict of interestThe authors have no financial interest to disclose in relation to the content of this article.
(© The Author(s) under exclusive licence to Biomedical Engineering Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Databáze: MEDLINE
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