Open Access
International Journal of Molecular Sciences, volume 21, issue 15, pages 5567
Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization
Alexandrushkina Natalia A
1, 2
,
Nimiritsky Peter
1, 2
,
Eremichev Roman
1
,
Popov Vladimir
2
,
Arbatskiy Mikhail
2
,
Danilova Natalia
1
,
Malkov Pavel
1, 2
,
Akopyan Zhanna
1, 2
,
Tkachuk Vsevolod
1, 2
,
Makarevich Pavel I
1, 2
Publication type: Journal Article
Publication date: 2020-08-04
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 16616596, 14220067
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Abstract
We report a comparative study of multipotent mesenchymal stromal cells (MSC) delivered by injection, MSC-based cell sheets (CS) or MSC secretome to induce healing of cutaneous pressure ulcer in C57Bl/6 mice. We found that transplantation of CS from adipose-derived MSC resulted in reduction of fibrosis and recovery of skin structure with its appendages (hair and cutaneous glands). Despite short retention of CS on ulcer surface (3–7 days) it induced profound changes in granulation tissue (GT) structure, increasing its thickness and altering vascularization pattern with reduced blood vessel density and increased maturation of blood vessels. Comparable effects on GT vascularization were induced by MSC secretome, yet this treatment has failed to induce repair of skin with its appendages we observed in the CS group. Study of secretome components produced by MSC in monolayer or sheets revealed that CS produce more factors involved in pericyte chemotaxis and blood vessel maturation (PDGF-BB, HGF, G-CSF) but not sprouting inducer (VEGF165). Analysis of transcriptome using RNA sequencing and Gene Ontology mapping found in CS upregulation of proteins responsible for collagen binding and GT maturation as well as fatty acid metabolism enzymes known to be negative regulators of blood vessel sprouting. At the same time, downregulated transcripts were enriched by factors activating capillary growth, suggesting that in MSC sheets paracrine activity may shift towards matrix remodeling and maturation of vasculature, but not activation of blood vessel sprouting. We proposed a putative paracrine trigger mechanism potentially rendering an impact on GT vascularization and remodeling. Our results suggest that within sheets, MSC may change their functional state and spectrum of soluble factors that influence tissue repair and induce more effective skin healing inclining towards regeneration and reduced scarring.
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Alexandrushkina N. A. et al. Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization // International Journal of Molecular Sciences. 2020. Vol. 21. No. 15. p. 5567.
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Alexandrushkina N. A., Nimiritsky P., Eremichev R., Popov V., Arbatskiy M., Danilova N., Malkov P., Akopyan Z., Tkachuk V., Makarevich P. I. Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization // International Journal of Molecular Sciences. 2020. Vol. 21. No. 15. p. 5567.
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TY - JOUR
DO - 10.3390/ijms21155567
UR - https://doi.org/10.3390%2Fijms21155567
TI - Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization
T2 - International Journal of Molecular Sciences
AU - Eremichev, Roman
AU - Arbatskiy, Mikhail
AU - Danilova, Natalia
AU - Malkov, Pavel
AU - Akopyan, Zhanna
AU - Tkachuk, Vsevolod
AU - Alexandrushkina, Natalia A
AU - Nimiritsky, Peter
AU - Popov, Vladimir
AU - Makarevich, Pavel I
PY - 2020
DA - 2020/08/04 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 5567
IS - 15
VL - 21
SN - 1661-6596
SN - 1422-0067
ER -
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@article{2020_Alexandrushkina,
author = {Roman Eremichev and Mikhail Arbatskiy and Natalia Danilova and Pavel Malkov and Zhanna Akopyan and Vsevolod Tkachuk and Natalia A Alexandrushkina and Peter Nimiritsky and Vladimir Popov and Pavel I Makarevich},
title = {Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization},
journal = {International Journal of Molecular Sciences},
year = {2020},
volume = {21},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {aug},
url = {https://doi.org/10.3390%2Fijms21155567},
number = {15},
pages = {5567},
doi = {10.3390/ijms21155567}
}
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MLA
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Alexandrushkina, Natalia A., et al. “Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization.” International Journal of Molecular Sciences, vol. 21, no. 15, Aug. 2020, p. 5567. https://doi.org/10.3390%2Fijms21155567.