Exploring standards for industrializing human induced pluripotent stem cells

Abstract

Popular belief assumes that human pluripotent cells can now be obtained in any lab or company by induced pluripotent stem (iPS) cell reprogramming. However, the difficulties in robustly producing human iPS-derived cells that are fit for drug discovery are becoming increasingly apparent. This is because we still have not come up with a strict definition of pluripotency. Our attempts at prospectively identifying differentiation-defective human iPS cells using teratoma assays or marker expression have clearly failed to date. Here, we will revisit how conventional pluripotency tests have failed in evaluating iPS cells adequately for drug discovery and emphasize two aspects of developmental transitions (what we call here a cell's chronological value and the segregation of factors as it differentiates) to elucidate inherent problems with our current understanding of human iPS cells. Finally, we challenge the field by presenting our perspective on distinguishing good human iPS cells from bad ones.