Many Kinds of Pluripotent Stem Cells, Which are Better for What?

Written by Norio Nakatsuji

Human pluripotent stem cell (PSC) lines are valuable resources for regenerative medicine and drug discovery

Human pluripotent stem cell (PSC) lines are valuable resources for regenerative medicine and drug discovery. There used to be only ES cell lines derived from pre-implantation embryos. Then, iPS cell lines were created by Professor Yamanaka with reprogramming of somatic cells. Around that time, scientists were examining distinct differences between mouse and human ES and iPS cells, and found that the former represents more primitive naive type of PSCs and the latter the epiblast-like primed type. However, it has been not easy to obtain stable naive human PSC lines that might be more useful for clinical application. Now, there is the latest progress toward it, a paper reported by Prof Austin Smith and others in Cell.

As a scientist working on mouse, monkey and human ES cell lines, I know many difficulties, such as slower growth rate and higher sensitivity to dissociation and other cell stresses, in handling monkey and human ES cells when compared to mouse ES cells. Thus, if the stable and transgene-less naive hPSC lines are present, it might be much better than conventional hPSC lines for production of large-scale cell products in many applications such as cell-based therapy.

In addition, there are several other types of PSC lines, and we should keep in mind that some of them may become a better option for some application in the future. One is the SCNT-ES cell lines derived from “cloned” human embryos, which seem to have more perfectly reprogrammed nuclei. Their derivation, however, requires human oocytes and skilled micro-manipulation, and thus, is not so easily. Another is ES cell lines from parthenogenic embryos, which have diploid chromosomes but only from oocyte. Thus, their gene function probably has differences from usual somatic cells, but homogeneity in HLA genes might be useful for giving better histocompatibility matching for larger populations. Also, they are derived from oocytes, which should be more acceptable for certain people than from embryos.

I should not forget to add that there are many kinds of the reprogramming factors to make iPS cell lines from also many kinds of somatic cells. First, several combinations of the reprogramming genes are known. Those factors can be delivered as integrating trans-genes, non-integrating episomal genes, mRNA, or proteins. Lastly, chemical compounds are used for reprogramming. Quality of the derived iPSC lines with these different factors are being compared each other.

If you are not in the stem cell field, some of you might worry that many types of PSC lines cause wasteful duplication of developing valuable technologies for how to utilize such stem cell lines. Fortunately, however, almost all methods, such as for cell growth, differentiation into useful cell types, etc., are generally the same or requires only minor modification. Thus, we can chose any types of hPSC lines if we find some better for certain purpose. In other words, we should not restrict our efforts too early to only one particular PSC type.