The present disclosure describes novel hybrid soluble ActRIIB-ECD polypeptides. The present disclosure provides methods for treating or preventing muscle wasting, bone disease, a metabolic, fibrosis, an autoimmune/inflammatory, cardiovascular disease, cancer or cancer, chronic kidney disease (CKD), arthritis, anorexia, liver disease, organ or tissue transplant rejection, anemia, pain, and/or aging in a subject in need thereof. Further, the present disclosure provides methods of inducing stem cell growth for tissue repair or organ regeneration in a subject. The aforementioned methods comprising administering to the subject a therapeutically effective amount of a hybrid ActRIIB ligand trap polypeptide. The present disclosure also provides pharmaceutical compositions comprising hybrid ActRIIB ligand trap polypeptides.
