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embryonic stem cells
Wednesday 25 June 2008
When allowed to differentiate in culture, ES cells generate colonies known as embryoid bodies (EBs) that contain a broad spectrum of cell types representing derivatives the three primary germ layers.
Support for the ES differentiation system as a valid model of embryonic development has come from studies demonstrating that the molecular and cellular events associated with the establishment of lineages such as the hematopoietic, endothelial, neural and skeletal muscle show striking similarities in the EBs and the early embryo.
The ES/EB model has been particularly useful in elucidating the early events involved in the development of the hematopoietic system and has enabled the identification of a progenitor with characteristics of the hemangioblast, the putative precursor of the hematopoietic and endothelial lineages.
These progenitors, known as blast colony forming cells (BL-CFC), arise within two to four days of EB differentiation and express the tyrosine kinase receptor Flk1.
They generate colonies with hematopoietic, endothelial and vascular smooth muscle in methylcellulose cultures in response to vascular endothelial growth factor (VEGF).
These characteristics suggest that the BL-CFC could represent the in vitro equivalent of the yolk sac hemangioblast and as such, the earliest commitment step in the differentiation of mesoderm to the hematopoietic and endothelial lineages.
Allografts
Human ES cells and their differentiated progeny express highly polymorphic major histocompatibility complex (MHC) molecules that serve as major graft rejection antigens to the immune system of allogeneic hosts.
To achieve sustained engraftment of donor cells, strategies are needed to overcome graft rejection without broadly suppressing host immunity. At least two types of strategies are pursued:
The first one is to create a patient-specific ES cell line if we may.
The second is to reduce or avoid graft rejection by using an existing hES cell line in a large hES cell bank with a closest match of MHC molecules.
The parthenogenesis and the somatic cell nuclear transfer (SCNT) represent two major strategies for generating histocompatible hES cells potentially for therapeutic use. To 2010, human SCNT has not been successfully used to generate a hES cell line.