Stem cell technology is undergoing a rapid development for its high potential in versatile therapeutic applications. Patent protection is a vital factor affecting the development and commercial success of life sciences inventions; yet human stem cells-based inventions have been encountering significant restrictions particularly in the perspective of patentable subject matters. This article looks into the patentability limits and unique challenges for human stem cells-based patents in four regions: Europe, the United States, China and Japan. We will also provide suggestions for addressing the emerging issues in each region.