Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation

Abstract Background Cell sheet technology has been identified as a promising approach for the construction of tissue-engineered vascular grafts (TEVGs). However, concerns regarding immunogenicity and ethical issues, which are raised by the use of fetal bovine serum (FBS) in traditional culture syste...

Full description

Saved in:
Bibliographic Details
Main Authors: Jing Yang, Xuheng Sun, Hongjing Jiang, Jiandong Li, Jierong Liang, Zhanyi Lin
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Biological Engineering
Subjects:
Online Access:https://doi.org/10.1186/s13036-025-00522-y
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850242874539507712
author Jing Yang
Xuheng Sun
Hongjing Jiang
Jiandong Li
Jierong Liang
Zhanyi Lin
author_facet Jing Yang
Xuheng Sun
Hongjing Jiang
Jiandong Li
Jierong Liang
Zhanyi Lin
author_sort Jing Yang
collection DOAJ
description Abstract Background Cell sheet technology has been identified as a promising approach for the construction of tissue-engineered vascular grafts (TEVGs). However, concerns regarding immunogenicity and ethical issues, which are raised by the use of fetal bovine serum (FBS) in traditional culture systems, limit its potential for clinical translation. Serum-free medium (SFM) has emerged as a safer and more controllable alternative, but further validation is required to determine its effectiveness and superiority in generating high-quality cell sheets. Methods This study systematically compared cell sheets generated under SFM and 10% FBS culture conditions in terms of structure, cellular phenotype, and functional properties. The expression levels of α-SMA and SM22, markers of vascular smooth muscle cells(VSMCs), were evaluated using immunofluorescence staining, qRT-PCR, and Western blot analysis to assess cellular phenotype. Histological staining and mechanical testing were employed to compare the morphology and mechanical properties of the cell sheets, while extracellular matrix (ECM) deposition and biochemical characteristics were also analyzed. Results Under SFM conditions, cells exhibited significantly higher α-SMA and SM22 expression levels (qRT-PCR showed a 1.8-fold and 2-fold increase, respectively; ****p < 0.0001) with clearer cytoskeletal arrangement. Cell sheets formed in SFM displayed comparable area(ns, p > 0.05), thickness(**p < 0.01), and mechanical properties to those cultured in 10% FBS, while ECM deposition was significantly enhanced (collagen content increased by approximately 40%, **p < 0.01). Furthermore, histological analysis revealed that cell sheets generated under SFM conditions were more compact and uniform, exhibiting superior structural organization. Conclusion SFM facilitates the generation of cell sheets that exhibit structural and functional properties analogous to those cultured in FBS. Additionally, SFM promotes cellular phenotype transition and ECM deposition. Consequently, SFM provides a safer, more controllable, and clinically translatable solution for cell sheet construction. Graphical Abstract
format Article
id doaj-art-3b200d14fc734a7cb63a84b5b760a8f5
institution OA Journals
issn 1754-1611
language English
publishDate 2025-05-01
publisher BMC
record_format Article
series Journal of Biological Engineering
spelling doaj-art-3b200d14fc734a7cb63a84b5b760a8f52025-08-20T02:00:09ZengBMCJournal of Biological Engineering1754-16112025-05-0119111310.1186/s13036-025-00522-ySerum-free endothelial cell culture medium for vascular smooth muscle cells sheet formationJing Yang0Xuheng Sun1Hongjing Jiang2Jiandong Li3Jierong Liang4Zhanyi Lin5School of Medicine, South China University of TechnologyGuangdong Cardiovascular InstituteSchool of Medicine, South China University of TechnologyJIHUA LaboratoryJIHUA LaboratorySchool of Medicine, South China University of TechnologyAbstract Background Cell sheet technology has been identified as a promising approach for the construction of tissue-engineered vascular grafts (TEVGs). However, concerns regarding immunogenicity and ethical issues, which are raised by the use of fetal bovine serum (FBS) in traditional culture systems, limit its potential for clinical translation. Serum-free medium (SFM) has emerged as a safer and more controllable alternative, but further validation is required to determine its effectiveness and superiority in generating high-quality cell sheets. Methods This study systematically compared cell sheets generated under SFM and 10% FBS culture conditions in terms of structure, cellular phenotype, and functional properties. The expression levels of α-SMA and SM22, markers of vascular smooth muscle cells(VSMCs), were evaluated using immunofluorescence staining, qRT-PCR, and Western blot analysis to assess cellular phenotype. Histological staining and mechanical testing were employed to compare the morphology and mechanical properties of the cell sheets, while extracellular matrix (ECM) deposition and biochemical characteristics were also analyzed. Results Under SFM conditions, cells exhibited significantly higher α-SMA and SM22 expression levels (qRT-PCR showed a 1.8-fold and 2-fold increase, respectively; ****p < 0.0001) with clearer cytoskeletal arrangement. Cell sheets formed in SFM displayed comparable area(ns, p > 0.05), thickness(**p < 0.01), and mechanical properties to those cultured in 10% FBS, while ECM deposition was significantly enhanced (collagen content increased by approximately 40%, **p < 0.01). Furthermore, histological analysis revealed that cell sheets generated under SFM conditions were more compact and uniform, exhibiting superior structural organization. Conclusion SFM facilitates the generation of cell sheets that exhibit structural and functional properties analogous to those cultured in FBS. Additionally, SFM promotes cellular phenotype transition and ECM deposition. Consequently, SFM provides a safer, more controllable, and clinically translatable solution for cell sheet construction. Graphical Abstracthttps://doi.org/10.1186/s13036-025-00522-ySerum freeCell sheetVascular smooth muscle cellsExtracellular matrixTissue-engineered vascular grafts
spellingShingle Jing Yang
Xuheng Sun
Hongjing Jiang
Jiandong Li
Jierong Liang
Zhanyi Lin
Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation
Journal of Biological Engineering
Serum free
Cell sheet
Vascular smooth muscle cells
Extracellular matrix
Tissue-engineered vascular grafts
title Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation
title_full Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation
title_fullStr Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation
title_full_unstemmed Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation
title_short Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation
title_sort serum free endothelial cell culture medium for vascular smooth muscle cells sheet formation
topic Serum free
Cell sheet
Vascular smooth muscle cells
Extracellular matrix
Tissue-engineered vascular grafts
url https://doi.org/10.1186/s13036-025-00522-y
work_keys_str_mv AT jingyang serumfreeendothelialcellculturemediumforvascularsmoothmusclecellssheetformation
AT xuhengsun serumfreeendothelialcellculturemediumforvascularsmoothmusclecellssheetformation
AT hongjingjiang serumfreeendothelialcellculturemediumforvascularsmoothmusclecellssheetformation
AT jiandongli serumfreeendothelialcellculturemediumforvascularsmoothmusclecellssheetformation
AT jierongliang serumfreeendothelialcellculturemediumforvascularsmoothmusclecellssheetformation
AT zhanyilin serumfreeendothelialcellculturemediumforvascularsmoothmusclecellssheetformation