Stanford University stem cell scientists who analyzed and compared human embryonic stem cells (hESCs) with human induced pluripotent stem cells (hiPSCs) in a new study reported that there are significant differences, including “a less stable pluripotent state” in hiPSCs that could render them less useful for tissue regeneration.
hESCs are derived from embryos, making them ethically controversial, while iPSCs are derived from reprogrammed somatic (body) cells. Both have the ability to generate a variety of tissue cells and “behave in a functionally similar manner,” according to the authors, led by Joseph Wu.
The researchers compared hESCs to hiPSCs that had been rigorously validated using several assays: microarrays, quantitative PCR (qPCR), immunocytochemistry, karyotyping, and teratoma formation.
Comparing the iPSCs to the “gold standard” blastocyst-derived pluripotent hESCs, the researchers noted that hiPSCs are “in vitro constructs that only partially recapitulate hESC biology.”
There are a number of similarities between the two types of cells, they said. hiPSCs “maintain a similar gene expression profile to hESCs, express high levels of pluripotency-related transcripts and cell surface antigens, and are capable of generating endothelial progenitor cells, beating cardiomyocytes, and teratomas containing all three germ layers.”
But hIPSCs also show some crucial differences, compared to hESCs, that “may limit their ultimate clinical applicability.”
HiPSCs, for example, showed “markedly more heterogeneity in gene expression levels … suggesting that hiPSCs occupy an alternate, less stable pluripotent state.”
In addition, HIPSCs displayed “slower growth kinetics and impaired directed differentiation as compared with hESCs.”
The authors concluded that “microfluidic single cell gene expression profiling can uncover instability in hiPSC gene expression profiles, which may significantly affect the ultimate clinical translatability of these exciting sources for cellular repair.”
Their findings, the authors wrote, are important to consider “when thinking about using these cells for the purpose of regenerative medicine.”
The study was published on February 7, 2011, in the Journal of Clinical Investigation.
Citation: “Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells;” Kazim H. Narsinh, et al.; Journal of Clinical Investigation, 7 February 2011, DOI:10.1172/JCI44635.,
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Contact: Joseph C. Wu, 650-736-2246, joewu@stanford.edu
