Fig 2: EUG-BMSC-EVs protected TSCs against H2O2 via Nrf2/HO-1 signaling pathway. (a–c) Western blot was used to examine the expression of NRF2 and HO-1 in H2O2-treated TSCs. (d, e) The expression of Nfe2l2 and HO-1 genes. (f) CCK8 assay was performed to assess TSC viability after ML385 treatment. (g, h) Apoptosis of the TSCs after ML385 treatment was detected by flow cytometry. (i, j) The intracellular ROS accumulation was detected by immunofluorescence assay after ML385 treatment. (k, l) Western blot was used to examine the expression of PCNA, catalase, SOD, PARP1, SCXA, TNMD, TNC, COLI, NRF2, and HO-1 after ML385 treatment. (m) The expression of PCNA, Cat, Sod1, SCX, TNMD, TNC, Col1a1, Nfe2l2, and HO-1 genes after ML385 treatment. Bars: 500 µm. Data are represented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001.

Fig 3: Histological analysis of CTS patients’ biopsies.Transverse carpal ligament (TCL) tissues collected from controls (n = 2) and Family 1 patients (n = 3) were analyzed. a H&E staining reveals collagen fragmentation, edema (asterisk), and vascular structures (arrows) in patients. b–d Immunostainings indicate lipomatosis (perilipin) and fibrosis (a-SMA and type III collagen) in patients’ TCLs. e Transmission electron microscopy (TEM) reveals a number of ectopic small fibrils and contrast difference in patients’ extracellular matrix (ECM). Source data are provided as a Source Data file.

Fig 4: Exogenous mitochondria successfully transplanted into damaged tenocytes enhance tenocyte-related marker levels and decrease MMP1 level. (A) Representative fluorescence images of tenocytes showing endogenous mitochondria (MitoTracker Green) and increased doses (1, 5, 25 µg) of exogenous mitochondria (MitoTracker CMXROS red) with DAPI nuclear staining (blue). Red fluorescent signal intensity increased dose dependently. (B–D) Gene expression of (B) TNMD, (C) COL1, and (D) MMP1 (GAPDH as loading control). (E–G) Representative western blots and densitometric quantification of (E) TNMD, (F) COL1, (G) MMP1 (ß-actin as loading control). Data represent mean ± standard deviation (SD) (n = 3). # p < 0.05 between TNF-a (+) group (black) and TNF-a (-) group as control (white), * p < 0.05 between MT (+) group damaged by TNF-a (gray) and MT (-) group damaged by TNF-a (black) TNF-a, tumor necrosis factor-a; MT, mitochondria; TNMD, tenomodulin; COL, collagen; MMP1, matrix metalloproteinase-1.

Fig 5: IL-10 activates Stat3 but has no effect on Akt expression in TDSCs. (A) Rat TDSCs were treated with the indicated concentrations of IL-10 and were subjected to western blot analysis to detect p-Stat3, Stat3, p-Akt and Akt protein expression. (B) TDSCs were treated with the indicated concentrations of IL-10 with or without the Stat3 inhibitor WP1066 and subjected to western blot analysis for Col1, Tnmd and Col3 protein expression. Data are expressed as the mean ± standard error of the mean. *P<0.05, **P<0.01 vs. 10 ng/ml IL-10. IL-10, interleukin-10; TDSCs, tendon-derived stem cells; p-, phosphorylated; Stat3, Signal transducer and activator of transcription 3; Akt, protein kinase B; Tnmd, tenomodulin; Col3, collagen type 3.