Methods of promoting stem cell proliferation by contacting the cells with cardiotrophin-1 (CT-1) are provided. The methods may further include contacting the stem cells with one or more stem cell modulators that promote differentiation of the stem cells. Methods of inhibiting stem cell proliferation by contacting the cells with one or more CT-1 inhibitor are also provided. The methods can be used to promote or inhibit stem cell proliferation in vitro and in vivo. Therapeutic applications of the methods in the replacement of damaged or defective tissue or in the inhibition of inappropriate cell proliferation are also provided.
