The experts define the embryonic stem cells (ESCs) as cells obtained from a blastocyst (conceived in a laboratory by in vitro insemination) which have the potential or capability to form or give origin to many types of specialized cells in the human body. 

This is important because, in recent years, the researchers have determined that most “incurable diseases” are due to the incapability of certain cells from recovering themselves from damage or to be in insufficient quantities. By discovering that certain cells can help to repair those damages or to restore a right number of cells, the experts have concluded that they can certainly treat a lot of those diseases with the stem cells.

However, it is very difficult to artificially create an adequate number of cells to treat all the people with this type of diseases worldwide. Hence, it is very important to know the stem cell differentiation process and the best way to trigger it in a laboratory.

There are clinical trials dated before 1999, which indicate that there are many protocols that can be used to stimuli the embryonic cells differentiation and, until now, it is still very controversial to determine which one of them is the best. Likewise, most of these protocols must be optimized for generating a particular cellular lineage.

The experts say that they have discovered 3 basic methods to promote the embryonic stem cell differentiation, which includes the formation of embryoid bodies (EBs, three-dimensional aggregates), the culture of embryonic stem cells as monolayers on extracellular matrix proteins and the culture of embryonic stem cells directly on supportive stromal layers.

Each one of these methods is effective, but they have different advantages and disadvantages. For example, the formation of embryoid bodies has the advantage of developing a three-dimensional structure which can make the cell–cell interactions between the new cells and the patients’ tissues easier. However, this method has the disadvantage that, as the three-dimensional structure is so complex, the production and release of certain cytokines necessary for its development can alter the signals interpretation by the embryonic stem cells and compromise the development of the type or lineage of cells needed by the patient.

The culture of embryonic stem cells as monolayers on extracellular matrix proteins is considered the simplest protocol because it consists in using different proteins to induce the differentiation of embryonic stem cells, and the obtained cells can be easily separated from the neighbor structures (including other cells and stroma). However, it is very important to say that the type and amount of proteins can widely affect the survival and developing of the different cell types obtained.

For its part, the culture of embryonic stem cells directly on supportive stromal layers is an excellent option in some cases because it can help to increase the growth of the cells obtained from the pluripotential stem cells. But, it has the disadvantage that can be less specific in the type of cells obtained from the differentiation stimuli. 

In other terms, it is an excellent method to induce the cells to grow, but it can be very unspecific in the type or lineage of cells that will be finally obtained in the laboratory. This method has another disadvantage, which is the fact that separating the obtained cells from the stromal cells can be very difficult for the expert.

Finally, it is very important to say that embryonic stem cells remain as pluripotential stem cells under the influence of certain factors, and only when these stimuli are suspended, the stem cells differentiate into progenitor cells derivate from the three embryonic germ layers (mesoderm, endoderm and ectoderm).

By using these 3 basic methods, the researchers have been able to create a very wide spectrum of cell types properly functional. However, this last point is the most difficult to demonstrate, especially in humans, due to ethical reasons, which is considered one of the major challenges in this field nowadays.

At this point, it is very important to say that, as it can be understood from the above, even when embryonic stem cells have the advantage of being pluripotential and differentiate into multiple cell types, this “plasticity” makes it very difficult for researchers to stimulate them to form a specific cell type. So, more research in this area is still needed.

In fact, from the mesoderm-derived lineages, the following types of cells can be included: hematopoietic, vascular, cardiac. Although more types of cells can be obtained, these 3 are considered the easiest to generate and, in consequence, the more studied.

In any case, the experts recommend considering 3 criteria during lineage-specific differentiation from embryonic stem cells. In the first place, the researcher must select and pre-stablish the protocols needed for promoting an efficient and reproducible development of the cell type of interest.

In the second place, lineage development from embryonic stem cells should recapitulate the developmental program that establishes the lineage in the early embryo. And finally, the mature cells obtained from any of these protocols or methods must be properly functional both in culture and when transplanted to the patient (or an experimental animal if it is the case).

In conclusion, every day the experts develop more knowledge about the reproduction of highly specialized cell populations from embryonic stem cells even when the use of this type of stem cells is still very controversial. 

There are many things not completely clear to date about these stem cells, but new researches have shown that certain somatic cells can be reprogrammed to act as embryonic cells, which is a very important finding because it can help to end the ethical problems related to this technique.

Finally, the use of lineage-specific progenitors must be used as a control or group of comparison to determine which of the cells integrate best into the adult tissues and determine which of them provide the most benefit for the patient. 


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