Adipose tissue‐derived extracellular matrix hydrogels as a release platform for secreted paracrine factors
Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue‐derived ECM hydrogels as release platform for factors secreted by adipos...
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| Veröffentlicht in: | Journal of tissue engineering and regenerative medicine Jg. 13; H. 6; S. 973 - 985 |
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| Sprache: | Englisch |
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England
John Wiley & Sons, Inc
01.06.2019
John Wiley and Sons Inc |
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| ISSN: | 1932-6254, 1932-7005, 1932-7005 |
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| Abstract | Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue‐derived ECM hydrogels as release platform for factors secreted by adipose‐derived stromal cells (ASCs). Lipoaspirates from nondiabetic and diabetic donors were decellularized. Finely powdered acellular ECM was evaluated for cell remainders and DNA content. Acellular ECM was digested, and hydrogels were formed at 37°C and their viscoelastic relaxation properties investigated. Release of ASC‐released factors from hydrogels was immune assessed, and bio‐activity was determined by fibroblast proliferation and migration and endothelial angiogenesis. Acellular ECM contained no detectable cell remainders and negligible DNA contents. Viscoelastic relaxation measurements yielded no data for diabetic‐derived hydrogels due to gel instability. Hydrogels released several ASC‐released factors concurrently in a sustained fashion. Functionally, released factors stimulated fibroblast proliferation and migration as well as angiogenesis. No difference between nondiabetic and diabetic hydrogels in release of factors was measured. Adipose ECM hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing‐related processes by releasing factors in a controlled way. |
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| AbstractList | Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue-derived ECM hydrogels as release platform for factors secreted by adipose-derived stromal cells (ASCs). Lipoaspirates from nondiabetic and diabetic donors were decellularized. Finely powdered acellular ECM was evaluated for cell remainders and DNA content. Acellular ECM was digested, and hydrogels were formed at 37°C and their viscoelastic relaxation properties investigated. Release of ASC-released factors from hydrogels was immune assessed, and bio-activity was determined by fibroblast proliferation and migration and endothelial angiogenesis. Acellular ECM contained no detectable cell remainders and negligible DNA contents. Viscoelastic relaxation measurements yielded no data for diabetic-derived hydrogels due to gel instability. Hydrogels released several ASC-released factors concurrently in a sustained fashion. Functionally, released factors stimulated fibroblast proliferation and migration as well as angiogenesis. No difference between nondiabetic and diabetic hydrogels in release of factors was measured. Adipose ECM hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing-related processes by releasing factors in a controlled way.Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue-derived ECM hydrogels as release platform for factors secreted by adipose-derived stromal cells (ASCs). Lipoaspirates from nondiabetic and diabetic donors were decellularized. Finely powdered acellular ECM was evaluated for cell remainders and DNA content. Acellular ECM was digested, and hydrogels were formed at 37°C and their viscoelastic relaxation properties investigated. Release of ASC-released factors from hydrogels was immune assessed, and bio-activity was determined by fibroblast proliferation and migration and endothelial angiogenesis. Acellular ECM contained no detectable cell remainders and negligible DNA contents. Viscoelastic relaxation measurements yielded no data for diabetic-derived hydrogels due to gel instability. Hydrogels released several ASC-released factors concurrently in a sustained fashion. Functionally, released factors stimulated fibroblast proliferation and migration as well as angiogenesis. No difference between nondiabetic and diabetic hydrogels in release of factors was measured. Adipose ECM hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing-related processes by releasing factors in a controlled way. Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue-derived ECM hydrogels as release platform for factors secreted by adipose-derived stromal cells (ASCs). Lipoaspirates from nondiabetic and diabetic donors were decellularized. Finely powdered acellular ECM was evaluated for cell remainders and DNA content. Acellular ECM was digested, and hydrogels were formed at 37°C and their viscoelastic relaxation properties investigated. Release of ASC-released factors from hydrogels was immune assessed, and bio-activity was determined by fibroblast proliferation and migration and endothelial angiogenesis. Acellular ECM contained no detectable cell remainders and negligible DNA contents. Viscoelastic relaxation measurements yielded no data for diabetic-derived hydrogels due to gel instability. Hydrogels released several ASC-released factors concurrently in a sustained fashion. Functionally, released factors stimulated fibroblast proliferation and migration as well as angiogenesis. No difference between nondiabetic and diabetic hydrogels in release of factors was measured. Adipose ECM hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing-related processes by releasing factors in a controlled way. |
| Author | Getova, Vasilena Harmsen, Martin C. Liguori, Gabriel R. Sharma, Prashant K. Dongen, Joris A. Stevens, Hieronymus P. Brouwer, Linda A. Lei, Berend |
| AuthorAffiliation | 6 Bergman Clinics Heerenveen, Zwolle, and Groningen The Netherlands 1 Department of Pathology and Medical Biology University of Groningen, University Medical Center Groningen Groningen The Netherlands 4 Department of Biomedical Engineering University of Groningen, University Medical Center Groningen Groningen The Netherlands 2 Department of Plastic Surgery University of Groningen, University Medical Center Groningen Groningen The Netherlands 3 Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM‐11) Heart Institute (InCor), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo Sao Paulo Brazil 5 Bergman Clinics Den Haag The Netherlands |
| AuthorAffiliation_xml | – name: 4 Department of Biomedical Engineering University of Groningen, University Medical Center Groningen Groningen The Netherlands – name: 2 Department of Plastic Surgery University of Groningen, University Medical Center Groningen Groningen The Netherlands – name: 6 Bergman Clinics Heerenveen, Zwolle, and Groningen The Netherlands – name: 1 Department of Pathology and Medical Biology University of Groningen, University Medical Center Groningen Groningen The Netherlands – name: 3 Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM‐11) Heart Institute (InCor), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo Sao Paulo Brazil – name: 5 Bergman Clinics Den Haag The Netherlands |
| Author_xml | – sequence: 1 givenname: Joris A. orcidid: 0000-0002-4366-0653 surname: Dongen fullname: Dongen, Joris A. organization: University of Groningen, University Medical Center Groningen – sequence: 2 givenname: Vasilena surname: Getova fullname: Getova, Vasilena organization: University of Groningen, University Medical Center Groningen – sequence: 3 givenname: Linda A. surname: Brouwer fullname: Brouwer, Linda A. organization: University of Groningen, University Medical Center Groningen – sequence: 4 givenname: Gabriel R. surname: Liguori fullname: Liguori, Gabriel R. organization: Heart Institute (InCor), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo – sequence: 5 givenname: Prashant K. surname: Sharma fullname: Sharma, Prashant K. organization: University of Groningen, University Medical Center Groningen – sequence: 6 givenname: Hieronymus P. surname: Stevens fullname: Stevens, Hieronymus P. organization: Bergman Clinics – sequence: 7 givenname: Berend surname: Lei fullname: Lei, Berend organization: Bergman Clinics – sequence: 8 givenname: Martin C. surname: Harmsen fullname: Harmsen, Martin C. email: m.c.harmsen@umcg.nl organization: University of Groningen, University Medical Center Groningen |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30808068$$D View this record in MEDLINE/PubMed |
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| Keywords | wound healing decellularization acellular matrix growth factors hydrogel mesenchymal stem cells |
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| SubjectTerms | acellular matrix Adipose tissue Adipose Tissue - metabolism Angiogenesis Animals Cattle Cell Proliferation - drug effects Culture Media, Conditioned - pharmacology decellularization Deoxyribonucleic acid Diabetes Diabetes mellitus Diabetes Mellitus - pathology DNA Elasticity Extracellular matrix Extracellular Matrix - drug effects Extracellular Matrix - metabolism Fibroblasts Fibroblasts - drug effects Fibroblasts - metabolism Glycosaminoglycans - metabolism growth factors Human Umbilical Vein Endothelial Cells - cytology Human Umbilical Vein Endothelial Cells - drug effects Humans hydrogel Hydrogels Hydrogels - chemistry Mesenchymal stem cells Neovascularization, Physiologic - drug effects Paracrine Communication - drug effects Paracrine signalling Reconstructive surgery Regeneration Regenerative medicine Stability Stromal cells Stromal Cells - drug effects Stromal Cells - metabolism Sulfates - metabolism Tissue engineering Viscoelasticity Viscosity Wound healing |
| Title | Adipose tissue‐derived extracellular matrix hydrogels as a release platform for secreted paracrine factors |
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