Patient-specific pluripotent stem cells: promises and challenges

Tissue transplantation is a well-established tool for the treatment of degenerative and malignant disorders, yet its use in clinical practice is hampered by the need for human-leukocyte-antigen-compatible donors and a shortage of suitable graft tissue. The discovery of human embryonic stem cells a decade ago raised hopes that a universal resource for the cell-based treatment of various conditions would soon become available. Embryonic stem cells derived by somatic-cell nuclear transfer or parthenogenesis can provide human-leukocyte-antigen-matched cells, which may be transplanted without the need for immunosuppressive treatment. However, technical hurdles and ethical concerns about use of oocytes and involvement of embryos have limited the clinical use of these cells. An alternative approach involves adult somatic cells being reprogrammed to enter a pluripotent state. Such manipulation of these readily available cells has enabled derivation of patient-specific, pluripotent stem-cell lines, without progression through the blastocyst stage. This Review critically analyzes the currently available methods for the generation of pluripotent stem cells, and discusses prospects for their clinical use.