Self-Assembled DNA Composite-Engineered Mesenchymal Stem Cells for Improved Skin-Wound Repair
Zhuoting Li 1, Yiming Wang 1, Hong Wang 2,
Haiyan Wang 1, Yingxu Shang 2, Shihua Wang 1, Qin Han 1, Jing Li 1, Robert
Chunhua Zhao 1, Qiao Jiang 2 3, Baoquan Ding 2 3 4
Small. 2024 Mar 5:e2310241. doi:
10.1002/smll.202310241.
PMID: 38441385
Abstract
The direct use of mesenchymal stem cells
(MSCs) as therapeutics for skin injuries is a promising approach, yet it still
faces several obstacles, including limited adhesion, retention, and engraftment
of stem cells in the wound area, as well as impaired regenerative and healing functions.
Here, DNA-based self-assembled composites are reported that can aid the
adhesion of MSCs in skin wounds, enhance MSC viability, and accelerate wound
closure and re-epithelialization. Rolling-circle amplification (RCA)-derived
DNA flowers, equipped with multiple copies of cyclic Arg-Gly-Asp (cRGD)
peptides and anti-von Willebrand factor (vWF) aptamers, act as robust
scavengers of reactive oxygen species (ROS) and enable synergistic recognition
and adhesion to stem cells and damaged vascular endothelial cells. These DNA
structure-aided stem cells are retained at localized wound sites, maintain
repair function, and promote angiogenesis and growth factor secretion. In both
normal and diabetes-prone db/db mice models with excisional skin injuries, facile
topical administration of DNA flower-MSCs elicits rapid blood vessel formation
and enhances the sealing of the wound edges in a single dose. DNA
composite-engineered stem cells warrant further exploration as a new strategy
for the treatment of skin and tissue damage.