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SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells

1
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland
2
Department of Biomedical Science, Royal College of Surgeons in Ireland, Adliya, P.O. Box 15503 Manama, Bahrain
3
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
4
Advanced Materials and Bioengineering Research Centre, Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin 2, Ireland
*
Author to whom correspondence should be addressed.
Biomedicines 2021, 9(2), 160; https://doi.org/10.3390/biomedicines9020160
Received: 4 January 2021 / Revised: 17 January 2021 / Accepted: 18 January 2021 / Published: 6 February 2021
(This article belongs to the Section Gene and Cell Therapy)
Non-healing diabetic foot ulcers (DFUs) can lead to leg amputation in diabetic patients. Autologous stem cell therapy holds some potential to solve this problem; however, diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen–chondroitin sulfate (coll–CS) scaffold, functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold), can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). We assessed the impact of the gene-activated scaffold on diabetic ADSCs by comparing their response against healthy ADSCs cultured on a gene-free scaffold over two weeks. Overall, we found that the gene-activated scaffold could restore the pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream β-arrestin signaling, as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also exhibited pro-wound healing features characterized by active matrix remodeling of the provisional fibronectin matrix and basement membrane protein collagen IV. The gene-activated scaffold also induced a controlled pro-healing response in the healthy ADSCs by disabling early developmental factors signaling while promoting the expression of tissue remodeling components. Conclusively, we show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs, paving the way for autologous stem cell therapies combined with novel biomaterials to treat DFUs. View Full-Text
Keywords: gene-activated scaffold; SDF-1α; human diabetic ADSCs; angiogenesis; wound healing gene-activated scaffold; SDF-1α; human diabetic ADSCs; angiogenesis; wound healing
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MDPI and ACS Style

Laiva, A.L.; O’Brien, F.J.; Keogh, M.B. SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells. Biomedicines 2021, 9, 160. https://doi.org/10.3390/biomedicines9020160

AMA Style

Laiva AL, O’Brien FJ, Keogh MB. SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells. Biomedicines. 2021; 9(2):160. https://doi.org/10.3390/biomedicines9020160

Chicago/Turabian Style

Laiva, Ashang L., Fergal J. O’Brien, and Michael B. Keogh 2021. "SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells" Biomedicines 9, no. 2: 160. https://doi.org/10.3390/biomedicines9020160

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