Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments
Adipose tissue-derived microvascular fragments (MVF) are used as vascularization units in tissue engineering. In this study, we investigated whether the vascularization capacity of MVF can be improved by systemic low-dose erythropoietin (EPO) administration. MVF were isolated from the epididymal fat...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2021-03-01
|
Series: | Journal of Tissue Engineering |
Online Access: | https://doi.org/10.1177/20417314211000304 |
_version_ | 1819122278317686784 |
---|---|
author | Thomas Später Denise MS Worringer Maximilian M Menger Michael D Menger Matthias W Laschke |
author_facet | Thomas Später Denise MS Worringer Maximilian M Menger Michael D Menger Matthias W Laschke |
author_sort | Thomas Später |
collection | DOAJ |
description | Adipose tissue-derived microvascular fragments (MVF) are used as vascularization units in tissue engineering. In this study, we investigated whether the vascularization capacity of MVF can be improved by systemic low-dose erythropoietin (EPO) administration. MVF were isolated from the epididymal fat of donor mice and seeded onto collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects within dorsal skinfold chambers of recipient mice. Both donor and recipient mice were treated daily with either EPO (500 IU/kg) or vehicle (0.9% NaCl). The implants were analyzed by stereomicroscopy, intravital fluorescence microscopy, histology, and immunohistochemistry. EPO-treated MVF contained a comparable number of proliferating Ki67 + but less apoptotic cleaved caspase-3 + endothelial cells when compared to vehicle-treated controls. Moreover, EPO treatment accelerated and improved the in vivo vascularization, blood vessel maturation, and epithelialization of MVF-seeded matrices. These findings indicate that systemic low-dose EPO treatment is suitable to enhance the viability and network-forming capacity of MVF. |
first_indexed | 2024-12-22T06:49:55Z |
format | Article |
id | doaj.art-aafdcc979b5f4788aca473be8ba63552 |
institution | Directory Open Access Journal |
issn | 2041-7314 |
language | English |
last_indexed | 2024-12-22T06:49:55Z |
publishDate | 2021-03-01 |
publisher | SAGE Publishing |
record_format | Article |
series | Journal of Tissue Engineering |
spelling | doaj.art-aafdcc979b5f4788aca473be8ba635522022-12-21T18:35:11ZengSAGE PublishingJournal of Tissue Engineering2041-73142021-03-011210.1177/20417314211000304Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragmentsThomas Später0Denise MS Worringer1Maximilian M Menger2Michael D Menger3Matthias W Laschke4Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, GermanyDepartment of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, Tuebingen, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, GermanyAdipose tissue-derived microvascular fragments (MVF) are used as vascularization units in tissue engineering. In this study, we investigated whether the vascularization capacity of MVF can be improved by systemic low-dose erythropoietin (EPO) administration. MVF were isolated from the epididymal fat of donor mice and seeded onto collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects within dorsal skinfold chambers of recipient mice. Both donor and recipient mice were treated daily with either EPO (500 IU/kg) or vehicle (0.9% NaCl). The implants were analyzed by stereomicroscopy, intravital fluorescence microscopy, histology, and immunohistochemistry. EPO-treated MVF contained a comparable number of proliferating Ki67 + but less apoptotic cleaved caspase-3 + endothelial cells when compared to vehicle-treated controls. Moreover, EPO treatment accelerated and improved the in vivo vascularization, blood vessel maturation, and epithelialization of MVF-seeded matrices. These findings indicate that systemic low-dose EPO treatment is suitable to enhance the viability and network-forming capacity of MVF.https://doi.org/10.1177/20417314211000304 |
spellingShingle | Thomas Später Denise MS Worringer Maximilian M Menger Michael D Menger Matthias W Laschke Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments Journal of Tissue Engineering |
title | Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments |
title_full | Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments |
title_fullStr | Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments |
title_full_unstemmed | Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments |
title_short | Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments |
title_sort | systemic low dose erythropoietin administration improves the vascularization of collagen glycosaminoglycan matrices seeded with adipose tissue derived microvascular fragments |
url | https://doi.org/10.1177/20417314211000304 |
work_keys_str_mv | AT thomasspater systemiclowdoseerythropoietinadministrationimprovesthevascularizationofcollagenglycosaminoglycanmatricesseededwithadiposetissuederivedmicrovascularfragments AT denisemsworringer systemiclowdoseerythropoietinadministrationimprovesthevascularizationofcollagenglycosaminoglycanmatricesseededwithadiposetissuederivedmicrovascularfragments AT maximilianmmenger systemiclowdoseerythropoietinadministrationimprovesthevascularizationofcollagenglycosaminoglycanmatricesseededwithadiposetissuederivedmicrovascularfragments AT michaeldmenger systemiclowdoseerythropoietinadministrationimprovesthevascularizationofcollagenglycosaminoglycanmatricesseededwithadiposetissuederivedmicrovascularfragments AT matthiaswlaschke systemiclowdoseerythropoietinadministrationimprovesthevascularizationofcollagenglycosaminoglycanmatricesseededwithadiposetissuederivedmicrovascularfragments |