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Anti-ageing protein β-Klotho rejuvenates diabetic stem cells for improved gene-activated scaffold based wound healing

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journal contribution
posted on 11.01.2022, 16:21 authored by Meenakshi Suku, Ashang Luwang Laiva, Fergal O'BrienFergal O'Brien, Michael B Keogh
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.

History

Comments

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

Published Citation

Suku M, Laiva AL, O'Brien FJ, Keogh MB. Anti-ageing protein β-Klotho rejuvenates diabetic stem cells for improved gene-activated scaffold based wound healing. J Pers Med. 2020;11(1):4

Publication Date

22 December 2020

PubMed ID

33375065

Department/Unit

  • 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)