A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction

<i>Introduction:</i> To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a...

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Main Authors: Xue Zhang, Jan Aart M. Schipper, Rutger H. Schepers, Johan Jansma, Fred K. L. Spijkervet, Martin C. Harmsen
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/12/1493
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author Xue Zhang
Jan Aart M. Schipper
Rutger H. Schepers
Johan Jansma
Fred K. L. Spijkervet
Martin C. Harmsen
author_facet Xue Zhang
Jan Aart M. Schipper
Rutger H. Schepers
Johan Jansma
Fred K. L. Spijkervet
Martin C. Harmsen
author_sort Xue Zhang
collection DOAJ
description <i>Introduction:</i> To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a platform to assess the interaction between skin-derived extracellular matrix (ECM) hydrogels and tSVF and their effects on their microenvironment in the first ten days of culture. <i>Material and Methods:</i> A tSVF mixed with ECM hydrogel was cultured for ten days. After 0, 3, 5, and 10 days of culture viability, histology, immunohistochemistry, gene expression, and collagen alignment and organization were assessed. <i>Results:</i> The viability analysis showed that tSVF remained viable during 10 days of culture and seemed to remain within their constitutive ECM. The fiber analysis demonstrated that collagen alignment and organization were not altered. No outgrowth of capillaries was observed in (immuno)histochemical staining. The gene expression analysis revealed that paracrine factors <i>TGFB1</i> and <i>VEGFA</i> did not change and yet were constitutively expressed. Pro-inflammatory factors <i>IL1B</i> and <i>IL6</i> were downregulated. Matrix remodeling gene <i>MMP1</i> was upregulated from day three on, while <i>MMP14</i> was upregulated at day three and ten. Interestingly, <i>MMP14</i> was downregulated at day five compared to day three while <i>MMP2</i> was downregulated after day zero. <i>Conclusions:</i> Skin-derived ECM hydrogels appear to be a versatile platform for investigating the function of a mechanically isolated adipose tissue stromal vascular fraction. In vitro tSVF remained viable for 10 days and sustained the expression of pro-regenerative factors, but is in need of additional triggers to induce vascularization or show signs of remodeling of the surrounding ECM. In the future, ECM-encapsulated tSVF may show promise for clinical administration to improve wound healing.
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spelling doaj-art-c837a2317e924b86aa53e148e93c3b1b2024-12-27T14:13:36ZengMDPI AGBiomolecules2218-273X2024-11-011412149310.3390/biom14121493A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular FractionXue Zhang0Jan Aart M. Schipper1Rutger H. Schepers2Johan Jansma3Fred K. L. Spijkervet4Martin C. Harmsen5Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands<i>Introduction:</i> To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a platform to assess the interaction between skin-derived extracellular matrix (ECM) hydrogels and tSVF and their effects on their microenvironment in the first ten days of culture. <i>Material and Methods:</i> A tSVF mixed with ECM hydrogel was cultured for ten days. After 0, 3, 5, and 10 days of culture viability, histology, immunohistochemistry, gene expression, and collagen alignment and organization were assessed. <i>Results:</i> The viability analysis showed that tSVF remained viable during 10 days of culture and seemed to remain within their constitutive ECM. The fiber analysis demonstrated that collagen alignment and organization were not altered. No outgrowth of capillaries was observed in (immuno)histochemical staining. The gene expression analysis revealed that paracrine factors <i>TGFB1</i> and <i>VEGFA</i> did not change and yet were constitutively expressed. Pro-inflammatory factors <i>IL1B</i> and <i>IL6</i> were downregulated. Matrix remodeling gene <i>MMP1</i> was upregulated from day three on, while <i>MMP14</i> was upregulated at day three and ten. Interestingly, <i>MMP14</i> was downregulated at day five compared to day three while <i>MMP2</i> was downregulated after day zero. <i>Conclusions:</i> Skin-derived ECM hydrogels appear to be a versatile platform for investigating the function of a mechanically isolated adipose tissue stromal vascular fraction. In vitro tSVF remained viable for 10 days and sustained the expression of pro-regenerative factors, but is in need of additional triggers to induce vascularization or show signs of remodeling of the surrounding ECM. In the future, ECM-encapsulated tSVF may show promise for clinical administration to improve wound healing.https://www.mdpi.com/2218-273X/14/12/1493stromal vascular fractionextracellular matrixMMPECMECM turnover
spellingShingle Xue Zhang
Jan Aart M. Schipper
Rutger H. Schepers
Johan Jansma
Fred K. L. Spijkervet
Martin C. Harmsen
A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction
Biomolecules
stromal vascular fraction
extracellular matrix
MMP
ECM
ECM turnover
title A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction
title_full A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction
title_fullStr A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction
title_full_unstemmed A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction
title_short A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction
title_sort versatile skin derived extracellular matrix hydrogel based platform to investigate the function of a mechanically isolated adipose tissue stromal vascular fraction
topic stromal vascular fraction
extracellular matrix
MMP
ECM
ECM turnover
url https://www.mdpi.com/2218-273X/14/12/1493
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