Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries
Peripheral nerve injuries often result in lifelong disabilities despite advanced surgical interventions, indicating the urgent clinical need for effective therapies. In order to improve the potency of adipose-derived stem cells (ASC) for nerve regeneration, the present study focused primarily on ex-...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/7/2/42 |
| _version_ | 1797568766729519104 |
|---|---|
| author | Katharina M. Prautsch Lucas Degrugillier Dirk J. Schaefer Raphael Guzman Daniel F. Kalbermatten Srinivas Madduri |
| author_facet | Katharina M. Prautsch Lucas Degrugillier Dirk J. Schaefer Raphael Guzman Daniel F. Kalbermatten Srinivas Madduri |
| author_sort | Katharina M. Prautsch |
| collection | DOAJ |
| description | Peripheral nerve injuries often result in lifelong disabilities despite advanced surgical interventions, indicating the urgent clinical need for effective therapies. In order to improve the potency of adipose-derived stem cells (ASC) for nerve regeneration, the present study focused primarily on ex-vivo stimulation of ASC by using growth factors, i.e., nerve growth factor (NGF) or vascular endothelial growth factor (VEGF) and secondly on fibrin-hydrogel nerve conduits (FNC) assisted ASC delivery strategies, i.e., intramural vs. intraluminal loading. ASC were stimulated by NGF or VEGF for 3 days and the resulting secretome was subsequently evaluated in an in vitro axonal outgrowth assay. For the animal study, a 10 mm sciatic nerve gap-injury was created in rats and reconstructed using FNC loaded with ASC. Secretome derived from NGF-stimulated ASC promoted significant axonal outgrowth from the DRG-explants in comparison to all other conditions. Thus, NGF-stimulated ASC were further investigated in animals and found to enhance early nerve regeneration as evidenced by the increased number of β-Tubulin III+ axons. Notably, FNC assisted intramural delivery enabled the improvement of ASC’s therapeutic efficacy in comparison to the intraluminal delivery system. Thus, ex-vivo stimulation of ASC by NGF and FNC assisted intramural delivery may offer new options for developing effective therapies. |
| first_indexed | 2024-03-10T20:01:46Z |
| format | Article |
| id | doaj.art-b64afa4a8b454f228efffef9e7cce32e |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-10T20:01:46Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-b64afa4a8b454f228efffef9e7cce32e2023-11-19T23:33:16ZengMDPI AGBioengineering2306-53542020-05-01724210.3390/bioengineering7020042Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-InjuriesKatharina M. Prautsch0Lucas Degrugillier1Dirk J. Schaefer2Raphael Guzman3Daniel F. Kalbermatten4Srinivas Madduri5Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4021 Basel, SwitzerlandDepartment of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4021 Basel, SwitzerlandDepartment of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4021 Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4021 Basel, SwitzerlandDepartment of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4021 Basel, SwitzerlandDepartment of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4021 Basel, SwitzerlandPeripheral nerve injuries often result in lifelong disabilities despite advanced surgical interventions, indicating the urgent clinical need for effective therapies. In order to improve the potency of adipose-derived stem cells (ASC) for nerve regeneration, the present study focused primarily on ex-vivo stimulation of ASC by using growth factors, i.e., nerve growth factor (NGF) or vascular endothelial growth factor (VEGF) and secondly on fibrin-hydrogel nerve conduits (FNC) assisted ASC delivery strategies, i.e., intramural vs. intraluminal loading. ASC were stimulated by NGF or VEGF for 3 days and the resulting secretome was subsequently evaluated in an in vitro axonal outgrowth assay. For the animal study, a 10 mm sciatic nerve gap-injury was created in rats and reconstructed using FNC loaded with ASC. Secretome derived from NGF-stimulated ASC promoted significant axonal outgrowth from the DRG-explants in comparison to all other conditions. Thus, NGF-stimulated ASC were further investigated in animals and found to enhance early nerve regeneration as evidenced by the increased number of β-Tubulin III+ axons. Notably, FNC assisted intramural delivery enabled the improvement of ASC’s therapeutic efficacy in comparison to the intraluminal delivery system. Thus, ex-vivo stimulation of ASC by NGF and FNC assisted intramural delivery may offer new options for developing effective therapies.https://www.mdpi.com/2306-5354/7/2/42adipose stem cellsneurotrophic factorsgrowth factorsperipheral nerve injuriesfibrin nerve conduitshydrogels |
| spellingShingle | Katharina M. Prautsch Lucas Degrugillier Dirk J. Schaefer Raphael Guzman Daniel F. Kalbermatten Srinivas Madduri Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries Bioengineering adipose stem cells neurotrophic factors growth factors peripheral nerve injuries fibrin nerve conduits hydrogels |
| title | Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries |
| title_full | Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries |
| title_fullStr | Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries |
| title_full_unstemmed | Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries |
| title_short | Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries |
| title_sort | ex vivo stimulation of adipose stem cells by growth factors and fibrin hydrogel assisted delivery strategies for treating nerve gap injuries |
| topic | adipose stem cells neurotrophic factors growth factors peripheral nerve injuries fibrin nerve conduits hydrogels |
| url | https://www.mdpi.com/2306-5354/7/2/42 |
| work_keys_str_mv | AT katharinamprautsch exvivostimulationofadiposestemcellsbygrowthfactorsandfibrinhydrogelassisteddeliverystrategiesfortreatingnervegapinjuries AT lucasdegrugillier exvivostimulationofadiposestemcellsbygrowthfactorsandfibrinhydrogelassisteddeliverystrategiesfortreatingnervegapinjuries AT dirkjschaefer exvivostimulationofadiposestemcellsbygrowthfactorsandfibrinhydrogelassisteddeliverystrategiesfortreatingnervegapinjuries AT raphaelguzman exvivostimulationofadiposestemcellsbygrowthfactorsandfibrinhydrogelassisteddeliverystrategiesfortreatingnervegapinjuries AT danielfkalbermatten exvivostimulationofadiposestemcellsbygrowthfactorsandfibrinhydrogelassisteddeliverystrategiesfortreatingnervegapinjuries AT srinivasmadduri exvivostimulationofadiposestemcellsbygrowthfactorsandfibrinhydrogelassisteddeliverystrategiesfortreatingnervegapinjuries |