SDF-1α gene-activated collagen scaffold enhances provasculogenic response in a coculture of human endothelial cells with human adipose-derived stromal cells

Abstract

Novel biomaterials can be used to provide a better environment for cross talk between vessel forming endothelial cells and wound healing instructor stem cells for tissue regeneration. This study seeks to investigate if a collagen scaffold containing a proangiogenic gene encoding for the chemokine stromal-derived factor-1 alpha (SDF-1α GAS) could be used to enhance functional responses in a coculture of human umbilical vein endothelial cells (HUVECs) and human adipose-derived stem/stromal cells (ADSCs). Functional responses were determined by (1) monitoring the amount of junctional adhesion molecule VE-cadherin released during 14 days culture, (2) expression of provasculogenic genes on the 14th day, and (3) the bioactivity of secreted factors on neurogenic human Schwann cells. When we compared our SDF-1α GAS with a gene-free scaffold, the results showed positive proangiogenic determination characterized by a transient yet controlled release of the VE-cadherin. On the 14th day, the coculture on the SDF-1α GAS showed enhanced maturation than its gene-free equivalent through the elevation of provasculogenic genes (SDF-1α—7.4-fold, CXCR4—1.5-fold, eNOS—1.5-fold). Furthermore, we also found that the coculture on SDF-1α GAS secretes bioactive factors that significantly (p < 0.01) enhanced human Schwann cells’ clustering to develop toward Bünger band-like structures. Conclusively, this study reports that SDF-1α GAS could be used to produce a bioactive vascularized construct through the enhancement of the cooperative effects between endothelial cells and ADSCs.

Immunomodulatory biomaterials on chemokine signaling in wound healing

“…CXCL12 is a chemokine known for its potent stem cell homing abilities, and application of both this chemokine and mimetics have been shown previously to stimulate wound healing (Badillo et al, 2007;Xu et al, 2022a). Another group integrated CXCL12 into their GAG therapeutic by using a hybrid polyethyleneimine (PEI)-CXCL12 containing collagen-chondroitin sulfate scaffold (Laiva et al, 2021).…”

Synthesis and characterization of a novel hydrogel based on carboxymethyl chitosan/sodium alginate with the ability to release simvastatin for chronic wound healing

“…The lymphangiogenic function increases with infiltrating macrophages that produce (VEGF-C) [35]. In addition to lymphangiogenesis, VEGF-C may regulate physiological angiogenesis [35,36]. Studies have also shown that SIM can suppress the growth of bacterial pathogens [37,38].…”

Anti-Aging β-Klotho Gene-Activated Scaffold Promotes Rejuvenative Wound Healing Response in Human Adipose-Derived Stem Cells

“…These charged nanoparticles are then soak-loaded into our coll-CS scaffold to generate the gene-activated scaffolds. Our previous studies have also shown that the PEI-based gene-activated scaffold can cause transient overexpression of the therapeutic transgene in a range of wound-healing cells and promote their regenerative abilities [21,24,25]. Traditionally, the gene-activated scaffold was developed to target host cells and promote local repair [26].…”