Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing
Skin wounds can lead to serious morbidity complications in diabetic patients due to the reduced healing potential of autologous stem cells. One reason for the low functional potency of stem cells from diabetic patients (diabetic stem cells) is attributed to their senescent-like nature. Here, we inve...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/1/4 |
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| author | Meenakshi Suku Ashang Luwang Laiva Fergal J. O’Brien Michael B. Keogh |
| author_facet | Meenakshi Suku Ashang Luwang Laiva Fergal J. O’Brien Michael B. Keogh |
| author_sort | Meenakshi Suku |
| collection | DOAJ |
| description | Skin wounds can lead to serious morbidity complications in diabetic patients due to the reduced healing potential of autologous stem cells. One reason for the low functional potency of stem cells from diabetic patients (diabetic stem cells) is attributed to their senescent-like nature. Here, we investigated if an anti-ageing protein, β-klotho, could be used to rejuvenate diabetic stem cells and to promote pro-angiogenic gene-activated scaffold (GAS)-induced functional response for wound healing applications. Human stem cells derived from the adipose tissue (adipose-derived stem cells (ADSCs)) of normal and diabetic (type 2) donors were used for the study. We report that the β-klotho priming facilitated inflammatory signal pruning by reducing interleukin-8 release by more than half while concurrently doubling the release of monocyte chemoattractant protein-1. Additionally, β-klotho priming enhanced the pro-angiogenic response of diabetic ADSCs on GAS by dampening the release of anti-angiogenic factors (i.e., pigment epithelium-derived factor, tissue inhibitor of metalloproteinase-1 and thrombospondin-1) while simultaneously supporting the expression of pro-angiogenic factors (i.e., Vascular Endothelial Growth Factor (VEGF), angiopoietin-2 and angiogenin). Finally, we show that β-klotho pre-treatment expedites the cellular expression of matrix proteins such as collagen IV and collagen VI, which are implicated in tissue maturation. Taken together, our study provides evidence that the synergistic effect of the pro-angiogenic GAS and β-klotho activation effectively accelerates the functional development of diabetic ADSCs for wound healing applications. |
| first_indexed | 2024-03-10T13:51:41Z |
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| id | doaj.art-ab41875a6c1342e3ac332d5582c10e71 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T13:51:41Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-ab41875a6c1342e3ac332d5582c10e712023-11-21T02:03:54ZengMDPI AGJournal of Personalized Medicine2075-44262020-12-01111410.3390/jpm11010004Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound HealingMeenakshi Suku0Ashang Luwang Laiva1Fergal J. O’Brien2Michael B. Keogh3Royal College of Surgeons in Ireland, Medical University of Bahrain, Kingdom of Bahrain P.O. Box 15503, IrelandRoyal College of Surgeons in Ireland, Medical University of Bahrain, Kingdom of Bahrain P.O. Box 15503, IrelandTissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, IrelandRoyal College of Surgeons in Ireland, Medical University of Bahrain, Kingdom of Bahrain P.O. Box 15503, IrelandSkin wounds can lead to serious morbidity complications in diabetic patients due to the reduced healing potential of autologous stem cells. One reason for the low functional potency of stem cells from diabetic patients (diabetic stem cells) is attributed to their senescent-like nature. Here, we investigated if an anti-ageing protein, β-klotho, could be used to rejuvenate diabetic stem cells and to promote pro-angiogenic gene-activated scaffold (GAS)-induced functional response for wound healing applications. Human stem cells derived from the adipose tissue (adipose-derived stem cells (ADSCs)) of normal and diabetic (type 2) donors were used for the study. We report that the β-klotho priming facilitated inflammatory signal pruning by reducing interleukin-8 release by more than half while concurrently doubling the release of monocyte chemoattractant protein-1. Additionally, β-klotho priming enhanced the pro-angiogenic response of diabetic ADSCs on GAS by dampening the release of anti-angiogenic factors (i.e., pigment epithelium-derived factor, tissue inhibitor of metalloproteinase-1 and thrombospondin-1) while simultaneously supporting the expression of pro-angiogenic factors (i.e., Vascular Endothelial Growth Factor (VEGF), angiopoietin-2 and angiogenin). Finally, we show that β-klotho pre-treatment expedites the cellular expression of matrix proteins such as collagen IV and collagen VI, which are implicated in tissue maturation. Taken together, our study provides evidence that the synergistic effect of the pro-angiogenic GAS and β-klotho activation effectively accelerates the functional development of diabetic ADSCs for wound healing applications.https://www.mdpi.com/2075-4426/11/1/4gene-activated scaffoldsβ-klothostem cells rejuvenationadipose-derived stem cellswound healing |
| spellingShingle | Meenakshi Suku Ashang Luwang Laiva Fergal J. O’Brien Michael B. Keogh Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing Journal of Personalized Medicine gene-activated scaffolds β-klotho stem cells rejuvenation adipose-derived stem cells wound healing |
| title | Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing |
| title_full | Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing |
| title_fullStr | Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing |
| title_full_unstemmed | Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing |
| title_short | Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing |
| title_sort | anti ageing protein β klotho rejuvenates diabetic stem cells for improved gene activated scaffold based wound healing |
| topic | gene-activated scaffolds β-klotho stem cells rejuvenation adipose-derived stem cells wound healing |
| url | https://www.mdpi.com/2075-4426/11/1/4 |
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