Both the use of animal products in culture medium and the poor definition of appropriate culture conditions have been major obstacles in establishing human embryonic stem cells (hESCs) suitable for use in clinical practice1. Now for the first time, a team led by Alan Colman, at ES Cell International in Singapore and Sydney IVF in Australia, has succeeded in generating six hESC lines designed for clinical use2.

To produce clinical-grade hESCs, the researchers followed stringent rules known as Good Manufacturing Practice (GMP). To ensure the embryos were ethically sound, the lead author, Jeremy Crook, and his colleagues aimed to adhere to current and future GMP standards, obtaining embryos from informed donors in line with international regulatory requirements.

The biological challenge was to culture embryos in the absence of live animal–derived products. This was achieved by manually extracting hESCs from the embryos (avoiding immunosurgery) and using GMP-manufactured products such as BSA-based serum replacement in the culture medium. From an initial 36 embryos, the team derived 8 hESC lines that were nonxenogeneic (free from animal biologics) and therefore valuable for cell transplantation. Some cells were banked for future use, and the remainder were used to characterize the cell lines.

Two of the cell lines were genetically abnormal and unsuitable for clinical use, although, in contrast to previous work3, the abnormality is not thought to be a result of culture conditions. To test the 'stemness' of the remaining lines, hESCs were injected into immunocompromised mice. The cells formed tumours containing ectoderm, endoderm and mesoderm—the three germ layers from which all other somatic cells are derived. In vitro differentiation of the hESCs showed that they had the potential to develop into precursor cells as diverse as cardiac and pancreatic. Finally, four cell lines were found to be free of a variety of human and nonhuman pathogens, with the remaining two still to be screened.

Colman and his team have taken a step toward stem cell therapy by developing a standardized protocol using approved reagents, materials and procedures to generate and characterize hESC lines of a clinical grade. Development of robust differentiation protocols and testing of the cells in animal models are the next hurdles in translating stem cell research from the bench to the development of cell-based therapies.