Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs
The application of endothelial progenitor cells (EPCs) for the revascularization of ischemic tissues, such as after myocardial infarction, stroke, and acute limb ischemia, has a huge clinical potential. However, the low retention and engraftment of EPCs as well as the poor survival of migrated stem...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253118302440 |
| _version_ | 1828355525753962496 |
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| author | Heidrun Steinle Sonia Golombek Andreas Behring Christian Schlensak Hans Peter Wendel Meltem Avci-Adali |
| author_facet | Heidrun Steinle Sonia Golombek Andreas Behring Christian Schlensak Hans Peter Wendel Meltem Avci-Adali |
| author_sort | Heidrun Steinle |
| collection | DOAJ |
| description | The application of endothelial progenitor cells (EPCs) for the revascularization of ischemic tissues, such as after myocardial infarction, stroke, and acute limb ischemia, has a huge clinical potential. However, the low retention and engraftment of EPCs as well as the poor survival of migrated stem cells in ischemic tissues still hamper the successful clinical application. Thus, in this study, we engineered, for the first time, murine EPCs with synthetic mRNAs to transiently produce proangiogenic factors vascular endothelial growth factor-A (VEGF-A), stromal cell-derived factor-1α (SDF-1α), and angiopoietin-1 (ANG-1). After the transfection of cells with synthetic mRNAs, significantly increased VEGF-A, SDF-1α, and ANG-1 protein levels were detected compared to untreated EPCs. Thereby, mRNA-engineered EPCs showed significantly increased chemotactic activity versus untreated EPCs and resulted in significantly improved attraction of EPCs. Furthermore, ANG-1 mRNA-transfected EPCs displayed a strong wound-healing capacity. Already after 12 hr, 94% of the created wound area in the scratch assay was closed compared to approximately 45% by untreated EPCs. Moreover, the transfection of EPCs with ANG-1 or SDF-1α mRNA also significantly improved the in vitro tube formation capacity; however, the strongest effect could be detected with EPCs simultaneously transfected with VEGF-A, SDF-1α, and ANG-1 mRNA. In the in vivo chicken chorioallantoic membrane (CAM) assay, EPCs transfected with ANG-1 mRNA revealed the strongest angiogenetic potential with significantly elevated vessel density and total vessel network length. In conclusion, this study demonstrated that EPCs can be successfully engineered with synthetic mRNAs encoding proangiogenic factors to improve their therapeutic angiogenetic potential in patients experiencing chronic or acute ischemic disease. Keywords: angiogenesis, EPCs, ischemia, proangiogenic factors, synthetic mRNA |
| first_indexed | 2024-04-14T02:43:44Z |
| format | Article |
| id | doaj.art-a9839a44c55943deb1acdee82638cc61 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-14T02:43:44Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-a9839a44c55943deb1acdee82638cc612022-12-22T02:16:39ZengElsevierMolecular Therapy: Nucleic Acids2162-25312018-12-0113387398Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAsHeidrun Steinle0Sonia Golombek1Andreas Behring2Christian Schlensak3Hans Peter Wendel4Meltem Avci-Adali5University Hospital Tuebingen, Department of Thoracic and Cardiovascular Surgery, Calwerstraße 7/1, 72076 Tuebingen, GermanyUniversity Hospital Tuebingen, Department of Thoracic and Cardiovascular Surgery, Calwerstraße 7/1, 72076 Tuebingen, GermanyUniversity Hospital Tuebingen, Department of Thoracic and Cardiovascular Surgery, Calwerstraße 7/1, 72076 Tuebingen, GermanyUniversity Hospital Tuebingen, Department of Thoracic and Cardiovascular Surgery, Calwerstraße 7/1, 72076 Tuebingen, GermanyUniversity Hospital Tuebingen, Department of Thoracic and Cardiovascular Surgery, Calwerstraße 7/1, 72076 Tuebingen, GermanyUniversity Hospital Tuebingen, Department of Thoracic and Cardiovascular Surgery, Calwerstraße 7/1, 72076 Tuebingen, Germany; Corresponding author: Meltem Avci-Adali, PhD, Department of Thoracic and Cardiovascular Surgery, University Hospital Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany.The application of endothelial progenitor cells (EPCs) for the revascularization of ischemic tissues, such as after myocardial infarction, stroke, and acute limb ischemia, has a huge clinical potential. However, the low retention and engraftment of EPCs as well as the poor survival of migrated stem cells in ischemic tissues still hamper the successful clinical application. Thus, in this study, we engineered, for the first time, murine EPCs with synthetic mRNAs to transiently produce proangiogenic factors vascular endothelial growth factor-A (VEGF-A), stromal cell-derived factor-1α (SDF-1α), and angiopoietin-1 (ANG-1). After the transfection of cells with synthetic mRNAs, significantly increased VEGF-A, SDF-1α, and ANG-1 protein levels were detected compared to untreated EPCs. Thereby, mRNA-engineered EPCs showed significantly increased chemotactic activity versus untreated EPCs and resulted in significantly improved attraction of EPCs. Furthermore, ANG-1 mRNA-transfected EPCs displayed a strong wound-healing capacity. Already after 12 hr, 94% of the created wound area in the scratch assay was closed compared to approximately 45% by untreated EPCs. Moreover, the transfection of EPCs with ANG-1 or SDF-1α mRNA also significantly improved the in vitro tube formation capacity; however, the strongest effect could be detected with EPCs simultaneously transfected with VEGF-A, SDF-1α, and ANG-1 mRNA. In the in vivo chicken chorioallantoic membrane (CAM) assay, EPCs transfected with ANG-1 mRNA revealed the strongest angiogenetic potential with significantly elevated vessel density and total vessel network length. In conclusion, this study demonstrated that EPCs can be successfully engineered with synthetic mRNAs encoding proangiogenic factors to improve their therapeutic angiogenetic potential in patients experiencing chronic or acute ischemic disease. Keywords: angiogenesis, EPCs, ischemia, proangiogenic factors, synthetic mRNAhttp://www.sciencedirect.com/science/article/pii/S2162253118302440 |
| spellingShingle | Heidrun Steinle Sonia Golombek Andreas Behring Christian Schlensak Hans Peter Wendel Meltem Avci-Adali Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs Molecular Therapy: Nucleic Acids |
| title | Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs |
| title_full | Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs |
| title_fullStr | Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs |
| title_full_unstemmed | Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs |
| title_short | Improving the Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs |
| title_sort | improving the angiogenic potential of epcs via engineering with synthetic modified mrnas |
| url | http://www.sciencedirect.com/science/article/pii/S2162253118302440 |
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