What could be the reason for the samples not clustering?
Samples will only cluster by experimental group if the experimental effect is large enough that it's the primary source of variance between your samples. If that's not the case then you'll get results like you're seeing. Whether that's a problem or not ends up depending on how large of an effect you expect to see. If your groups are different stages in differentiation or another large effect, then you expect that samples will cluster into groups. If you're looking at something like some large unaffected tissue in a disease vs. normal state then seeing a cloud of points is quit reasonable.