*2.3. Mouse MSCs Culture*

Gastrocnemius and cranial thigh muscles were collected from C57BL male mice (six weeks) and minced, digested with 1% pronase (Roche, Mannheim, Germany) for 1 h at 37 ◦C, and then centrifuged at 1000× *g* for 3 min followed by passage of the digested tissue phase through a 100 mm syringe filter (Millipore, Darmstadt, Germany). After centrifugation of the filtrate at 1000× *g* for 5 min, the pellets were suspended in DMEM + 20% FBS + 1% P/S + 5 ng/mL FGF2 (fibroblast growth factor 2, Miltenyi Biotec GmbH, Auburn, CA, USA), seeded on collagen-coated plates (Corning, Brooklyn, NY, USA), and incubated in a humidified 5% CO2 atmosphere at 37 ◦C. The medium was changed every day. For induction of MSC differentiation into muscle cells, media were switched to DMEM + 2% FBS + 1% P/S or DMEM + 1% P/S followed by incubation for two days. MSC purity was confirmed with Pax7 protein expression (Santa Cruz Biotechnology, Paso Robles, CA, USA) using immunocytochemistry.

#### *2.4. MTT Assay*

C2C12 cells were cultured with DMEM + 10% FBS + 1% P/S for two days for analysis of cell viability. The cells were washed with DMEM and then incubated with 0.5 mg/mL MTT reagent (Sigma Aldrich) for 1 h. After dissolving the formazan crystals with DMSO (Sigma Aldrich), absorbance was measured at 540 nm (Tecan Group Ltd., Männedorf, Switzerland).

#### *2.5. Immunoneutralization*

TTR protein neutralization was carried out with TTR-specific antibodies (5 μg/mL, Santa Cruz Biotechnology) for two or three days in DMEM + 2% FBS + 1% P/S or DMEM + 1% P/S differentiation media.

#### *2.6. Exosomes Isolation*

Cells were cultured with DMEM + 1% P/S differentiation media. The cells were incubated for two or three days and the media were then collected, centrifuged at 2000× *g* for 30 min, and the upper phase collected for exosomes isolation. Using a total exosomes isolation reagent (Thermo Fisher Scientific, MA, USA), the exosomes from the upper phase were isolated according to the manufacturer's protocol. In brief, the media were incubated with the total exosomes isolation reagent at 4 ◦C overnight and centrifuged at 10,000× *g* for 60 min. After discarding the supernatant, the pellet was dried at room temperature and suspended in PBS.

Mouse plasma (4 mL) was filtered with a 0.8 um syringe filter (Sartorius, Goettingen, Germany), and the exosomes were then isolated according to the manufacturer's protocol (exoEasy Maxi Kit, Qiagen, Germantown, MD, USA).
