Induced pluripotent stem (iPS) cells still fall short of embryonic stem (ES) cells, says a recent paper in the Proceedings of the National Academy of Sciences. Due to the inherent problems of ES cells concerning ethical retrieval, inefficiency in patient-specific medicine, and limited availability of contaminant-free cell lines, iPS cells—which are derived from reprogrammed adult cells—have long been heralded as a potential alternative. But recent research from the University of Wisconsin-Madison has demonstrated that iPS cells are markedly less efficient and predictable than ES cells. The study did not determine why iPS cells experience these problems, but concluded that no single reprogramming method was to blame.
Researchers from the laboratory of Su-Chun Zhang at the School of Medicine and Public Health at the University of Wisconsin-Madison compared the ability of ES cells and iPS cells to differentiate into human neurons in a laboratory setting. Though the researchers found that iPS cells could develop into all of the neural cells that their embryonic counterparts could, they did so with markedly reduced efficiency. Only some of the iPS cells differentiated as expected, which made them unpredictable compared to ES cells. "Embryonic stem cells can pretty much be predicted," said Zhang in a press release. "Induced cells cannot. That means that at this point, there is still some work to be done to generate ideal induced pluripotent stem cells for [clinical] applications."
The study compared the ability of five ES cell lines (H1, H9, H13, HSF-1.14, and ES103) and 12 iPS cell lines to differentiate into progenitor neural cells and the different types of functional neurons that make up the brain. The iPS cells lines were derived using lentiviral, retroviral and nonintegrating episomal methods. All of the iPS cell lines, regardless of how they were derived, used the same transcriptional network to generate neuroepithelia and appropriate neural tissue as ES cells, but failed to differentiate with the efficiency and predictability of the ES cell lines.
According to Zhang, the team expected that the iPS cells reprogrammed by inserting genes (lentiviral and retroviral methods) would behave less like ES cells because without foreign genes the iPS cells would essentially be identical to their embryonic counterparts. However, this was not the case; in fact, iPS cells’ behavior was varied and inefficient despite how they were reprogrammed. "It is totally surprising," said Zhang. "It tells us that all the techniques for generating induced pluripotent stem cells are still not optimal. There is room for improvement."
Despite their failure to stack up against ES cells, iPS cells still have important applications for stem cell research. According to Zhang, iPS cells are essential for creating pure populations of specific cell types, and as a model for pathological studies and therapeutic screening. Zhang was confident that iPS cells could be improved to achieve the same efficiency as ES cells. "It appears to be a technical issue," said Zhang. "Technical things can usually be overcome."
The research was funded by the National Institute of Neurological Disease and Stroke and the Amyotrophyic Lateral Sclerosis Association. The paper, “Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency,” was published Feb. 16.