Generation of Functionally Mature Erythrocytes From Human Pluripotent Stem Cells: A Review on Methodology

Abstract: The knowledge about the early development in human ontogeny has been greatly expanded by the establishment of human embryonic stem cell (hESC) lines and， recently， induced pluripotent stem cells (hiPSC). In the past decade， hESCs and hiPSCs have been proved good tools in characterization of molecular and cellular mechanisms controlling the normal and diseased differentiation of hematopoietic progenitors and mature， functional blood cells. Most of the types of hematopoietic cells (HCs) derived from hESCs have recently been shown with functionally mature properties， including erythrocytes， neutrophils， platelets， megakaryocytes， eosinophils， monocytes， dendritic cells (DC)， nature killer (NK) cells， mast cells (MCs) and B/T-lineage lymphoid cells. Along with the advances in research， a clinical translation of hESC/hiPSC-derived HCs as novel therapies has been foreseen in near future. However， different efficiencies in blood cell production have been reported when using different culture systems. We recently established efficient blood cell-inducing systems by co-culture of hESC/hiPSCs with murine fetal stromal cells. In our culture system， hESC/hiPSC-derived hematopoietic progenitors are further induced along to a specific blood cell lineage， such as erythrocytes， MCs and eosinophils， etc. We gained large quantity of purified erythrocytes with maturity and function. In this review， we illustrate the co-culture methods developed in our laboratory， along with many different methods developed by other groups， and the technique to induce hESC/hiPSCs to hematopoietic cells and mature erythrocytes. The direction and the problems urgently needing a breakthrough in future research are also addressed.

CSTR: 32200.14.cjcb.2012.11.0001