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SDF-1α gene-activated collagen scaffold restores pro-angiogenic wound healing features in human diabetic adipose-derived stem cells

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posted on 11.01.2022, 17:09 authored by Ashang L Laiva, Fergal O'BrienFergal O'Brien, Michael B Keogh
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.

Funding

RCSI Dilmun Ph.D. scholarship

History

Comments

The original article is available at https://www.mdpi.com/

Published Citation

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

Publication Date

6 February 2021

PubMed ID

33562165

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • RCSI Bahrain
  • Tissue Engineering Research Group (TERG)

Research Area

  • Immunity, Infection and Inflammation
  • Biomaterials and Regenerative Medicine
  • Chemistry and Pharmaceutical Sciences

Publisher

MDPI AG

Version

  • Published Version (Version of Record)