Best Practice & Research Clinical Obstetrics & Gynaecology
2The promise of human embryonic stem cells
Section snippets
Human embryonic stem cells—the beginning
At the blastocyst stage, the embryo forms an inner cell mass (ICM), which is capable of forming a wide range of body cell types, and an outer trophectoderm, which is committed to forming part of the placenta. In the early 1980s, Evans and Kaufman1 and Martin2 identified the potential that lies within the isolation and propagation of pluripotent cells of the blastocyst—the ICM. The mouse ICM was successfully isolated and propagated in an embryonic state under specific culture conditions,
Maintenance and self-renewal hESCs
Human ESCs are immortal cells, capable of perpetual self-renewal in culture while maintaining undifferentiated phenotype and normal karyotype. As noted earlier, hESCs were first derived and maintained in an undifferentiated state when cultured on inactivated mouse embryonic fibroblasts (MEFs) as feeder layer. However, unlike mouse ESCs, hESCs cannot be maintained in an undifferentiated state with the presence of leukemia inhibitor factor (LIF) in feeder-free conditions. In light of this
Differentiation of hESCs—the potential
HESCs are capable of developing into all three primary germ layer derivatives—ectoderm, mesoderm and endoderm—both in vitro and in vivo. Because of ethical restraints concerning the formation of chimeras from hESCs, the in vivo formation of teratoma is used to assess the developmental capabilities of specific hESC lines.4 Teratoma is a benign tumour that can be formed by the intramuscular or subcutaneous injection of hESCs into immunocompromised mice.4 Teratoma formed from pluripotent cells
Vascular differentiation and development from hESCs
From the earliest stages, the embryo develops in the absence of vascularization, receiving its nutrition by diffusion. In an orderly and sequential manner, however, the embryo rapidly transforms into a highly vascular organism, which depends for its survival on a functional, complex network of capillary plexuses and blood vessels.47 The process of blood vessel formation is referred to as ‘vasculogenesis’, in which endothelial cell (EC) precursors differentiate, expand and coalesce to form a
Future aspects—towards practice
Although hESCs holds great promise for future applications in regenerative medicine, there are two main obstacles: (1) the selection and expansion of pure populations of desired cell types; and (2) the immunological tolerance of allogenic cells. Different strategies are being examined, including genetic manipulation to abolish ‘un-behaved cells’50 and creating a ‘universal cell’, the major histocompatibility complex (MHC) of which will be suitable for all patients.52 Another approach involves
Acknowledgements
The hESC research in our lab was partly supported by NIH grants 1RO1HL073798-01 and 1R24RR018405-01. The authors thank Mrs Myrna Perlmutter for her help in the preparation of this paper.
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Perspectives of cell therapy in sequelae from cerebrovascular accidents
2012, NeurocirugiaRetinal Pigment Epithelium Derived from Embryonic Stem Cells
2008, Principles of Regenerative MedicineRetinal Pigment Epithelium Derived from Embryonic Stem Cells
2007, Principles of Regenerative MedicineModern stem cell therapy: approach to disease
2015, Wiener Klinische WochenschriftDerivation of human embryonic stem cells (hESC)
2014, Methods in Molecular Biology