dCas9-Based PDGFR-ß Activation ADSCs Accelerate Wound Healing in Diabetic Mice through Angiogenesis and ECM Remodeling.
Int J Mol Sci
; 24(6)2023 Mar 21.
Article
en En
| MEDLINE
| ID: mdl-36983022
ABSTRACT
The chronic wound represents a serious disease characterized by a failure to heal damaged skin and surrounding soft tissue. Mesenchymal stem cells (MSCs) derived from adipose tissue (ADSCs) are a promising therapeutic strategy, but their heterogeneity may result in varying or insufficient therapeutic capabilities. In this study, we discovered that all ADSCs populations expressed platelet-derived growth factor receptor ß (PDGFR-ß), while the expression level decreased dynamically with passages. Thus, using a CRISPRa-based system, we endogenously overexpressed PDGFR-ß in ADSCs. Moreover, a series of in vivo and in vitro experiments were conducted to determine the functional changes in PDGFR-ß activation ADSCs (AC-ADSCs) and to investigate the underlying mechanisms. With the activation of PDGFR-ß, AC-ADSCs exhibited enhanced migration, survival, and paracrine capacity relative to control ADSCs (CON-ADSCs). In addition, the secretion components of AC-ADSCs contained more pro-angiogenic factors and extracellular matrix-associated molecules, which promoted the function of endothelial cells (ECs) in vitro. Additionally, in in vivo transplantation experiments, the AC-ADSCs transplantation group demonstrated improved wound healing rates, stronger collagen deposition, and angiogenesis. Consequently, our findings revealed that PDGFR-ß overexpression enhanced the migration, survival, and paracrine capacity of ADSCs and improved therapeutic effects after transplantation to diabetic mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
/
Células Madre Mesenquimatosas
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
China