Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing

Area of Science:

• Regenerative Medicine
• Cell Biology
• Biotechnology

Background:

• Diabetic patients exhibit impaired wound healing due to reduced stem cell function.
• Diabetic stem cells often display a senescent-like phenotype, limiting their therapeutic potential.
• Gene-activated scaffolds (GAS) offer a promising approach for enhancing stem cell function.

Purpose of the Study:

• To investigate the rejuvenating effect of β-klotho on diabetic adipose-derived stem cells (ADSCs).
• To evaluate the synergistic potential of β-klotho and GAS in promoting pro-angiogenic responses for wound healing.
• To assess the impact of β-klotho on inflammatory and matrix protein expression in diabetic ADSCs.

Main Methods:

• Human ADSCs from normal and type 2 diabetic donors were isolated and characterized.
• ADSCs were primed with β-klotho, and their response on GAS was analyzed.
• Key inflammatory cytokines (e.g., interleukin-8), chemoattractants (e.g., monocyte chemoattractant protein-1), anti-angiogenic factors, pro-angiogenic factors (e.g., VEGF), and matrix proteins were quantified.

Main Results:

• β-klotho priming significantly reduced inflammatory interleukin-8 release and increased monocyte chemoattractant protein-1.
• Diabetic ADSCs treated with β-klotho showed enhanced pro-angiogenic activity on GAS, with reduced anti-angiogenic factors and increased pro-angiogenic factors.
• β-klotho pre-treatment accelerated the expression of crucial matrix proteins like collagen IV and VI.

Conclusions:

• β-klotho effectively rejuvenates diabetic ADSCs, mitigating their senescent-like characteristics.
• The combination of pro-angiogenic GAS and β-klotho activation synergistically enhances the functional capacity of diabetic ADSCs.
• This approach holds significant promise for accelerating functional development of diabetic ADSCs in wound healing applications.