0.22 m lter

All of the reagents used in this study were purchased from Sigma-Aldrich Company (St. Louis, MO, USA) unless stated otherwise. Milli-Q ultrapure water (Millipore, Bedford, MA, USA) was used for the preparation of solutions.
Self-made solutions were ltered through a 0.22-µm lter (Millipore) and stored at 4°C or at -20°C until use. Pipette tips, centrifuge tubes, and petri dishes were purchased in aseptic packages and were all disposable.
Preparation of "all-in-one" modi ed ABE vector
The sequence information of the modi ed ABE vector (namely as pCMV-ABEmaxAW) created by was obtained from the Addgene (catalog: #125647) (Rees. et al. 2019) . For construction of ABE vector, the ABEmaxAW fragment with AgeI/BglII restriction sites was obtained by gene synthesis (BGI, Shenzhen, China), and linked to the PX459 (Addgene catalog: #62988) vector according to our previous study (Wei et al. 2020 ). The accuracy of molecular cloning was tested by gene sequencing, and the obtained vector was named as PX-ABEmaxAW.
Complete sequence information of PX-ABEmaxAW weas provided online with this paper. The gRNA and ABE expression elements were integrated into one vector, namely as "all-in-one" vector. The "all-in-one" vector is very suitable for transfection of pig cells.

The concentrations of NGF in sciatic nerve tissue, BMSC-CM and cell culture medium were detected using an enzyme linked immunosorbent assay (ELISA) kit (USCN, USA) following manufacturer's instruction. Medium of cells were collected and ltered through a 0.22 µm lter (Millipore) for removing cell debris. Each sample were measured three times using a spectrophotometer with absorbance at 490 nm wavelength.

ESCs at 70% of con uence were incubated in DMEM/F12 containing 10% exosome-depleted FBS (System Biosciences, CA, USA) for 48 h. Subsequently, the medium of ESCs was collected and centrifuged at 2000 g for 10 min at 4 ℃ to eliminate cell debris. The resulting supernatants were ltered through a 0.22-µm lter (Millipore, Billerica, MA, USA) to remove microvesicles, and then concentrated through an Amicon Ultra-15 100 kDa centrifugal lter (Millipore, Billerica, MA, USA) at 4000 rpm for 30 min. Exosomes were then isolated using the Total Exosome Isolation kit (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's protocol. Brie y, the supernatant was mixed with Total Exosome Reagent and incubated for 24 h at 4°C. Samples were centrifuged at 10,000 x g for 2 h and the supernatant removed. The exosome pellet was re-suspended in 100 µL of PBS and stored at -80 ℃.

FBS was depleted of EVs by ultracentrifugation at 140,000 g and 4 °C for 16 hours, and the supernatant was collected and ltered using a 0.22 µm lter (Millipore, USA). EVs derived from blood samples and cell medium were isolated by differential centrifugation as previously described (15) . Before EV isolation, cells were cultured in normal medium until 50% con uency and then washed with phosphate-buffered saline (PBS) three times; and the medium was replaced with RPMI-1640 with 10% EV-depleted FBS and cultured under normoxic or hypoxic conditions. After 48 hours, the cell culture medium was harvested (50 ml), and EVs were isolated by differential centrifugation as previously described. The EVs were used immediately for further experiments. The size distribution and concentration of EVs were analysed by nanoparticle tracking analysis (NTA) using a ZetaView particle tracker from ParticleMetrix (Meerbusch, Germany). We used a transmission electron microscope (TEM; JEM-1200EX, JEOL Ltd., Japan) to observe the structure of EVs. CD63, CD81 and Alix were used as exosomal markers, and calnexin was used as a negative control for EVs. PKH67 (Sigma-Aldrich, USA) was used to label EVs. Twenty-four hours after PKH67labelled EVs were incubated with OSCC cells, DAPI was used for nuclei staining. The cells were visualized with a confocal uorescence microscope (Leica, Germany).

All of the reagents used in this study were purchased from Sigma-Aldrich Company (St. Louis, MO, USA) unless stated otherwise. Milli-Q ultrapure water (Millipore, Bedford, MA, USA) was used for the preparation of solutions.
Self-made solutions were ltered through a 0.22-µm lter (Millipore) and stored at 4°C or at -20°C until use. Pipette tips, centrifuge tubes, and petri dishes were purchased in aseptic packages and were all disposable.

Breast cancer tissues were splice into small pieces and digested with collagenase I for overnight, the cells were cultured and the conditioned medium were collected. Fibroblasts educated by TGF-β1 or cancer cells and the cell conditioned medium was collected. The conditioned medium was ltered through a 0.22-µm lter (Merck Millipore, Massachusetts, USA) to remove cellular debris, and then exosomes were extracted using the kit from Invitrogen.