MuVs, but not lmEVs, have an effect on MN survival, neurite length, and neurite branching, and on myotube survival. iPSC-MN or myotubes were treated with either MuVs or lmEVs secreted from the muscle cells of either ALS subjects or healthy subjects. (A) Motor neuron death as a percentage reduction in MN numbers compared to untreated MN (n = 3/4 per group). **, p < 0.01. (B) Measurements of neurite lengths per MN. *, **, ***, p < 0.05, p < 0.01 and p < 0.001 respectively, ns: non-significant. (C) Neurites of iPSC-MN cells had fewer neurite branch-points following treatment with ALS MuVs compared to treatment with healthy MuVs, while (D) no difference was observed in the effects of ALS lmEVs compared to healthy lmEVs; the D statistic and p-values are indicated for two-sample Kolmogorov–Smirnov tests (ALS vs. healthy MuVs, p = 0.00006; ALS vs. healthy lmEVs, p = 0.24). (E) Myotube death as a percentage reduction in myotube numbers compared to untreated myotubes (n = 3 per group). *, p < 0.05; ns—non-significant.