Human bmscs

Human BMSCs were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) and HUVECs were obtained from the Cell Bank of the Chinese Academy of Science (Shanghai, China). All cell lines were maintained at 37°C with 5% CO₂ in a humidified chamber. Modified Eagle's medium (MEM; Hyclone, Logan, UT, USA) containing 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin was used to cultivate the BMSCs. To validate the effect of IFN‐γ priming on BMSCs, when BMSCs reached 80% confluence, exosome‐free media supplemented with or without 25 ng/mL IFN‐γ was used to cultivate the cells for 48 h, and the conditioned medium (CM) was collected to extract exosomes (IExos and NExos). HUVECs were maintained in Dulbecco's MEM (Hyclone) supplemented with 10% FBS and 1% penicillin/streptomycin. To simulate hyperglycemic conditions, HUVECs were treated with HG (33 mM glucose) (Sigma‐Aldrich, St. Louis, MO, USA). The low‐glucose group (LG, 5.56 mM glucose + 27.44 mM mannitol) was used as a control. Exosomes (50 μg/mL) derived from BMSC‐CM under different conditions were co‐cultured with HUVECs.

All animal experiments were approved by the Animal Ethics Committee of Jinan University. Sprague-Dawley rats (female, eight weeks old) were obtained from the Medical Experimental Animal Center of Guangdong Province, randomly split into two groups, and then underwent sham operation (n = 10) and bilateral ovariectomy (n = 10) (Fig. S1a, b). Each rat received an intramuscular penicillin injection (80 000 units/rat) for three days after the operation. All rats were euthanized two months after the operation. The bone marrow of each rat was collected from bilateral femurs in an aseptic environment and separated by density gradient centrifugation at a speed of 1 200 r·min⁻¹. Then, BMSCs were cultured in alpha-modified Eagle’s medium (Gibco, Thermo Scientific, USA) with 10% fetal bovine serum (FBS, Gibco, Thermo Scientific, USA) and 1% penicillin and streptomycin (Gibco, USA) at 37 °C with 5% CO₂ and 95% humidity (Fig. S1c). The culture medium was replaced every three days. The expression of specific cell surface markers of BMSCs was verified (Fig. S1d)^{51 (link)}.
In addition, human BMSCs were purchased from the American Type Culture Collection (Manassas, USA) and cultured in alpha-modified Eagle’s medium (10% FBS and 1% penicillin and streptomycin) at 37 °C with 5% CO₂ and 95% humidity.

HEK293 cells and human BMSCs were purchased from the American Type Culture Collection (ATCC) cell bank (Manassas, USA) and cultured in Dulbecco's modified Eagle's medium (DMEM, HyClone, Logan, UT, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, Waltham, MA, USA), 100 U/mL penicillin, and 100 mg/mL streptomycin (Gibco) at 37°C, 5% CO₂, and saturated humidity.