A Biological Overview of Embryonic Stem Cells (ESCs)

Embryonic stem cells (ESCs) are a type of cell that comes from very early embryos, that is, before the embryo has implanted into the uterus, (pre-implantation stage embryo). They are typically found in the inner cell mass (ICM) of an embryo at the blastocyst stage.

Definition of ESCs

As the embryo undergoes its initial development, the cells do not differentiate, having the power to become almost any type of mature cell in the body. This is shown in Figure 1. The twin characteristics of ESCs are self-renewal and pluripotency, and these have made them very useful for in vitro applications.

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The History Behind Embryonic Stem Cells (ESCs)

It was more than three decades ago that the first ESCs were extracted from the ICM of a mouse embryo at the blastocyst stage, found to be capable of developing into any type of tissue, and called blastocyst ESCs. This led to the isolation of ESCs in a similar manner from all kinds of sources, including pre-implantation embryos, mammals such as sheep (1987), rabbits (1993), cattle (1994), pigs (1995), humans (1998) and rats (2008).

Various human embryonic stages have been exploited for this purpose, such as the blastocyst, the morula, the arrested blastocyst, and blastomeres. Another type is the ESC derived from human somatic cell embryos formed by nuclear transfer (SCNT), also called human nuclear transfer ESCs (NT-ESCs).

Features of ESCs

There are some unique characteristics of ESCs that have made them a sought-after species for the study of many biological applications. They include the fact that they can be easily expanded compared to other cells, and can differentiate into any type of mature cell of the original organism.

They are thus used to elicit disease mechanisms, to act as living prototypes of cell and organ development in vitro, to screen compounds for drug development, and for treatments based on cell replacements for diseased tissue.

Several techniques have been developed to resolve the constraints specific to ESCs and to enable better ESC derivation and growth in culture. With poor culture medium, the resulting ESC experiments are likely to show poor spontaneous differentiation and reproducibility. When MEK/ERK inhibition together with glycogen synthase kinase-3 (GSK3) inhibition was produced, while Stat3 activation by Leukemia Induced Factor (LIF HZ-1292) was carried out at the same time, the conditions were thought to be sufficient to encourage emerging ESCs to remain in their pluripotent ground state.

Now, however, the cells are cultured with basic Fibrosis Growth Factor (bFGF HZ-1285), which is better at encouraging self-renewal in human ESC cells. Such cultures are also generally supplied with the following:

  • Feeder cells, conditioned medium or cytokines like  TGF- HZ-1011, WNT3A HZ-1296
  • Human serum albumin (HSA HZ-3001) or serum replacement
  • Matrix components such as matrigel or fibronectin, or laminin

If a stem cell culture develops ill-effects due to the xenograft effects, such as the formation of toxic proteins or a higher chance of contamination with animal pathogens, or the development of complications in developmental studies, the hESC line may be switched to a controlled medium which uses only animal-free products, to obtain superior results.

Applications of Embryonic Stem Cells (ESCs)

Some ESC applications include research and therapy in cardiovascular conditions, spinal cord trauma and glaucoma. Shroff et al reported recently that the transplantation of hESCs to the site of injury of the spinal cord was followed by a significant betterment of body control, balance, limbus-associated movements and sensory function.

Another development is the ability to differentiate ESCs directly into the beta-cells of the pancreas that secrete insulin, which carry the GLUT2, INS1, GCK, and PDX1 markers, via PDX1-mediated epigenetic changes that cause cell reprogramming.

Human fibroblasts can also be directly converted to a variety of induced subtype neurons (iNCs) by causing neurogenic factors to be overexpressed. Being able to produce these as well as induced pluripotent stem cells (iPSCs) allows the development of various kinds of in vitro cell models and further insights into how neurons develop. This may be expected to reveal more about how degeneration occurs in the brain, and how cell replacement can be developed as a treatment for many disorders.

Overall, therefore, the spurt in the understanding of hESCs have brought bioengineering based on stem cells to the forefront of research interest, but the obstacles remain: for one, are hESCs really safe? Again, research in this field must mean overcoming ethical and even legal hindrances, since at present every established line of ESCs must be traced to a pre-implantation embryo.

References

  1. Establishment of pluripotential cell lines from haploid mouse embryos.
  2. Differentiation of pluripotent embryonic stem cells into cardiomyocytes.
  3. Stem Cell Bioengineering
  4. Establishment in culture of pluripotential cells from mouse embryos.
  5. Embryonic stem cell lines derived from human blastocysts.
  6. Towards the isolation of embryonal stem cell lines from the sheep.
  7. Pluripotency of cultured rabbit inner cell mass cells detected by isozyme analysis and eye pigmentation of fetuses following injection into blastocysts or morulae.
  8. Strategies for the isolation and characterization of bovine embryonic stem cells.
  9. Isolation of embryonic cell‐lines from porcine blastocysts.
  10. Embryonic stem cell lines derived from human blastocysts.
  11. Germline competent embryonic stem cells derived from rat blastocysts.
  12. A method to recapitulate early embryonic spatial patterning in human embryonic stem cells.
  13. The ground state of embryonic stem cell self-renewal.
  14. Derivation and characterization of mouse embryonic stem cells from permissive and nonpermissive strains.
  15. BMP4 initiates human embryonic stem cell differentiation to trophoblast.
  16. The impact of culture on epigenetic properties of pluripotent stem cells and pre-implantation embryos.
  17. Testing of nine different xeno-free culture media for human embryonic stem cell cultures.
  18. Human embryonic stem cells in the treatment of patients with spinal cord injury.
  19. Differentiation of Mouse Embryonic Stem Cells Towards Functional Pancreatic Beta-Cell Surrogates through Epigenetic Regulation of Pdx1 by Nitric Oxide.
  20. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts.
  21. Conversion of mouse and human fibroblasts into functional spinal motor neurons.
  22. MicroRNA-mediated conversion of human fibroblasts to neurons.
  23. Leukemia inhibitory factor promotes nestin-positive cells, and increases gp130 levels in the Parkinson disease mouse model of 6-hydroxydopamine.

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Last updated: Sep 13, 2018 at 6:25 AM

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