VEGFA-Enriched Exosomes from Tendon-Derived Stem Cells Facilitate Tenocyte Differentiation, Migration, and Transition to a Fibroblastic Phenotype

Abstract

Tendon-derived stem cells (TDSCs) play a vital role in repair of rotator cuff tear injuries by secreting paracrine proteins that regulate resident cell functions. Secreted exosomes may play a role in tendon injury repair by mediating intercellular communication; however, the detailed mechanisms by which TDSC-derived exosomes affect tenocyte development remain unknown. Here, we examined the effects of exosomes isolated from conditioned medium of TDSCs on tenocyte differentiation, migration, and transition to a fibroblastic phenotype in vitro. Successful isolation of exosomes from TDSCs was confirmed by high expression levels of CD81, CD63, CD9, and TSG101. Treatment with TDSC-derived exosomes promoted the growth and migration of cultured rat tenocytes, and increased the levels of the fibrosis markers collagen I, collagen III, scleraxis, tenascin C, and α-smooth muscle actin. Furthermore, vascular endothelial growth factor A (VEGFA) expression was higher in TDSC-derived exosomes than in TDSCs, and genetic knockdown of VEGFA suppressed the stimulatory effect of TDSC-derived exosomes on tenocyte development. Overall, these results demonstrate that VEGFA-enriched exosomes isolated from TDSCs promote differentiation and migration of cultured tenocytes and their transition to a fibroblastic phenotype. These data provide a new potential clinical treatment strategy for tendon injury.

Human serum‐derived exosomes modulate macrophage inflammation to promote VCAM1‐mediated angiogenesis and bone regeneration

“…Serum‐Exo robustly expressed exosome‐specific markers CD9, CD63, CD81 and TSG‐101. These results are according to results from the previous literature 23 . Serum‐Exo has been reported to regulate inflammation.…”

“…These results are according to results from the previous literature. 23 Serum‐Exo has been reported to regulate inflammation. Lu et al showed that serum‐Exo from tumour patients promotes macrophage inflammation.…”

Roxadustat promotes hypoxia‐inducible factor‐1α/vascular endothelial growth factor signalling to enhance random skin flap survival in rats

“…52 VEGF-A is considered a therapeutic target in various cancers based on its profound effects, 53 in cardiovascular diseases, 54 and in tendon injuries. 55 VEGF-A is a hypoxia-inducible protein 56 secreted by fibroblasts, 57 platelets, 58 neutrophils, 59 and endothelial cells. 60 VEGF-A regulates its tyrosine kinase receptors to stimulate the pathway.…”

“…VEGF is a protein family consisting of several members, including VEGF‐A, VEGF‐B, VEGF‐C, VEGF‐D, VEGF‐E, placental growth factor, and endocrine gland‐derived vascular endothelial growth factor 52 . VEGF‐A is considered a therapeutic target in various cancers based on its profound effects, 53 in cardiovascular diseases, 54 and in tendon injuries 55 . VEGF‐A is a hypoxia‐inducible protein 56 secreted by fibroblasts, 57 platelets, 58 neutrophils, 59 and endothelial cells 60 .…”

Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital

“…Furthermore, diverse regenerative medicine approaches have recently been investigated to improve tendinopathy management, including stem cell therapies, tissue graft bioengineering, and the use of orthobiologics [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Notably, recent regulatory shifts and quality-oriented constraints related to cytotherapies have prompted the deployment of important efforts toward the development of cell-derived and cell-free therapeutic management options for tendinopathies [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Parallelly, the medical use of autologous platelet-rich plasma (PRP) preparations in orthopedics and in sports medicine for tendon and ligament affections has drastically increased over the past two decades [ 23 , 24 , 25 , 26 , 27 ].…”