Tissue-engineered mesenchymal stem cell constructs alleviate tendinopathy by suppressing vascularization

Autor: Dijun Li, Jingwei Jiu, Haifeng Liu, Xiaojun Yan, Xiaoke Li, Lei Yan, Jing Zhang, Zijuan Fan, Songyan Li, Guangyuan Du, Jiao Jiao Li, Yanan Du, Wei Liu, Bin Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Bioactive Materials, Vol 36, Iss , Pp 474-489 (2024)
Druh dokumentu: article
ISSN: 2452-199X
DOI: 10.1016/j.bioactmat.2024.06.029
Popis: Tendinopathy leads to low-grade tissue inflammation and chronic damage, which progresses due to pathological imbalance in angiogenesis. Reducing early pathological vascularization may be a new approach in helping to regenerate tendon tissue. Conventional stem cell therapy and tissue engineering scaffolds have not been highly effective at treating tendinopathy. In this study, tissue engineered stem cells (TSCs) generated using human umbilical cord mesenchymal stem cells (hUC-MSCs) were combined with microcarrier scaffolds to limit excessive vascularization in tendinopathy. By preventing VEGF receptor activation through their paracrine function, TSCs reduced in vitro angiogenesis and the proliferation of vascular endothelial cells. TSCs also decreased the inflammatory expression of tenocytes while promoting their anabolic and tenogenic characteristics. Furthermore, local injection of TSCs into rats with collagenase-induced tendinopathy substantially reduced early inflammation and vascularization. Mechanistically, transcriptome sequencing revealed that TSCs could reduce the progression of pathological angiogenesis in tendon tissue, attributed to Rap1-mediated vascular inhibition. TSCs may serve as a novel and practical approach for suppressing tendon vascularization, and provide a promising therapeutic agent for early-stage clinical tendinopathy.
Databáze: Directory of Open Access Journals