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The promise of human embryonic stem cells

https://doi.org/10.1016/j.bpobgyn.2004.07.004Get rights and content

Pluripotency refers to the ability of a cell to give rise to cells that originate from all three germ layers. Among the available human pluripotent cells, human embryonic stem cells (hESCs) are considered to have the greatest probability for practical clinical application because of their simple propagation and stability in culture. Since their first derivation, issues concerning hESC maintenance and self-renewal have been widely addressed. The first part of this review presents the accumulated knowledge concerning the self-renewal of hESCs and discusses recent genetic profile data, which seem to shed light on hESC self-renewal and pluripotency mechanism. The second part deals with the regenerative potential of hESCs. Available lineage-specific differentiations of hESCs are presented, with detailed data on the ability of hESCs to differentiate into trophoblast cells, an observation that might broaden the definition of their developmental potential. Specific focus is given to vascular cell differentiation, including endothelial and smooth muscle cells. Transplantation limitations as well as current steps taken toward resolution conclude the review.

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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