When Woo Suk Hwang and his group at Seoul National University announced their creation of human stem cell lines that matched the donors’ own DNA, the media craze began. Surely this achievement marked the beginning of eagerly awaited tailor-made therapies for patients with spinal cord injuries, diabetes, Alzheimer disease, and a host of other congenital and acquired disorders. Or did it? Before patient-specific stem cells, or any other stem cells, can be used for human therapeutics, there are hurdles to overcome. These barriers in the translation of bench experiments to bedside remedies do not just include the obvious ethical, political, and funding problems that are so widely deliberated. The more relevant hurdles that stymie clinical stem cell therapies are the scientific ones — those that are often overlooked in the lay press, which contributes to public unawareness of just how far we still are from using stem cells in a clinically meaningful manner. Norio Nakatsuji is the director of the Institute for Frontier Medical Sciences at Kyoto University and is the only investigator in Japan whose laboratory creates human embryonic stem cell lines. Nakatsuji notes that before clinical trials can go forward, the production of these stem cell lines must be improved so that they are clinical-grade. The cells should be produced in a highly sterile facility, he says, using human feeder cells or a no–feeder cell protocol and culture media without animal serum or proteins. Although not currently available, Nakatsuji speculates that such clinical-grade human embryonic stem cells will be obtainable within a few years. But the future existence of these cells is still not the panacea some may think it is. “Just injecting stem cells is not going to work,” said Shahin Rafii, a physician and stem cell scientist at Cornell University Medical College. “First, you have to be able to differentiate the cells into functional, transplantable tissues. We don’t really know how to do this yet.” Directing the differentiation of the cells is just one obstacle. Scientists also do not know whether differentiated patient-specific stem cell lines would be immunologically tolerated by the donor/host or whether they would be safe or effective. Yet another problem is that stem cell lines created from patients with diseases will carry features of the disease and would likely not be useful for treating those patients. Beyond difficulties with the cells themselves, the adult tissue environment where the cells need to thrive also hinders the progression to clinical transplantation. “For cell therapy to work you need to be able to get the cells to engraft and expand after transplantation,” Marcus Grompe, a hepatic stem cell researcher at Oregon Health & Science University, told the JCI. “That part is very difficult and has not been solved at all for some key tissues . . . we are still several years away from clinical trials.” In order to be useful for treating neurodegenerative diseases, for example, the stem cells need to survive in the damaged and diseased brain, make proper synaptic connections, and form appropriate pathways for proper neural function. “We have no idea — at least not yet — of how to accomplish this feat,” said Steve Goldman, chief of the Division of Cell and Gene Therapy at University of Rochester Medical Center. “Making matters worse,” Goldman explained, “once a desired cell type is generated from an embryonic stem cell, its isolation to appropriate levels of purity is by no means straightforward.” Isolating pure stem cells is not foolproof, and remnant cells typically persist. These cells can generate a whole host of tumors even if they are completely diploid and genomically stable. Another issue, according to Rafii, is proper vascularization of these transplanted cells to ensure that their blood supply is adequate. Rafii said that it may be necessary to nanofabricate small blood vessels and put these into the cells before transplantation. Although no miracle cures have been found yet, these obstacles are not cause for pessimism. According to Charles Jennings, executive director of the Harvard Stem Cell Institute, “It is a fast-moving field. Human embryonic stem cells were just isolated in 1998. It’s still early.”