The Mesendoderm: A Wellspring of Cell Lineages for Regenerative Medicine

Regenerative medicine is centred around the premise that progenitor populations can be engineered to give rise to mature cell lineages forming a complex tissue architecture which in turn produces functional organs. The potency of the starting progenitor population is therefore a critical consideration. The mesendoderm is a rare population of cells present in the embryo only at gastrulation. This bipotent population gives rise to the mesoderm and the definitive endoderm and all mature cell types derived from these germ layers. Mesodermal progenitors generate cardiac, smooth and skeletal muscle, as well as the blood and vascular lineages, bone and connective tissue cells. The endoderm is the source of numerous cell lineages with potential utility for regenerative medicine including hepatocytes, pancreatic lineages and the epithelial cells of the respiratory, gastrointestinal and reproductive tracts. The development of numerous organs is dependent upon mesoderm-derived lineages interacting with endodermal-derived cell types. The kidney, adrenal gland, pancreas and genito-urinary tract development all require interactions between mesodermal and endodermal derivative cell types. Here, we describe the unique genetic programmes that lead to mesendoderm formation, the pathways leading to mesoderm and endoderm specification and examples where mature cell types from both germ layers interact to support their mutual development. We will also show how these programmes are being harnessed to direct the differentiation of pluripotent cells in vitro into mesendodermderived cells and tissues which can be used to improve the quality of human life. Finally, we will discuss considerations for combining stem cell differentiation with tissue engineering through 3D bioprinting modalities.

Keywords: 3D bioprinting, Embryonic development, Embryonic stem cells (ESC), Endoderm, Germ layer specification, Induced pluripotent stem cells (iPSC), Mesendoderm, Mesoderm, Regenerative medicine, Tissue engineering.