Stem Cells: Current and Future Applications – Part 3
The Future of Stem Cells Research
A large number of exciting and valuable research possibilities lie ahead for these cells. The future use of stem cells in their application in medicine and rehabilitation is vast. The following are but a few of these possible uses and areas of future research.
3-D Printed Stem Cells
The use of 3-D printing to produce actual usable products is taking off. Scientists are close to developing a 3-D printer that can produce usable human embryonic stem cells. Not too far in the future will potentially come a printer that produces viable tissue that can be differentiated into complete organs.
In fact, researchers at Heriot-Watt University in Edinburgh have used 3-D technology to produce embryonic cells. The printer they developed gently prints uniform size cell droplets that maintain their viability and ability to differentiate into various cell types. This original method can be used to print human tissue for testing new medications, growing organs, or possibly even printing live cells within the body.
Human embryonic stem cells are especially useful in regenerative medicine, replacing damaged or diseased tissue, cells, or even organs. Their ability to differentiate into any type of cell is the quality that makes them so useful.
In the laboratory, these cells are placed in a solution of biochemicals that stimulate them to develop into various other cells. This is called differentiation. In the beginning, these cells develop embryoid bodies. The 3-D printing process developed in Edinburgh can produce these embryoid bodies in specific sizes and shapes.
Evaluating these cells showed that 95 percent of them remained viable 24 hours after being printed. This showed they were not killed by the process of printing. Three days after printing, 89 percent of them were still viable. Further testing showed their pluripotency, or their ability to differentiate into other cells.
Engineering Stem Cells in Bioreactors
One of the accomplishments to be achieved in the future for these cells is to control their microenvironments, or niches, to determine what kind of cells they will differentiate into.
Many of the types of stem cells are capable of differentiating into many other types of cells. The ability to direct this differentiation into needed cell types will be a tremendous boon to the multitudinous uses of these cells.
Factors that regulate the differentiation process include physical forces brought to bear, oxygen supply, paracrine/autocrine signaling, and extracellular matrix. Developing bioreactors that will regulate these factors will greatly improve the efficiency of the differentiation process.
Recent efforts have led to the development of microfluidic devices and microbioreactors that provide significant mechanisms for making the microenvironment of stem cells as it needs to be for more efficient differentiation.
The development and use of novel bioreactors will greatly improve the efficacy of these cells as they are utilized in medical applications.
Another approach to directing the differentiation process of stem cells to effectively develop needed cell types is through the science of nanotechnology. The difficulty thus far in making the process of differentiation more efficient and effective for producing desired cell types has to do with the lack of understanding of the exact chemical and physical signals required in the process.
Using chemicals in the laboratory to direct this process has worked. Unfortunately, the results have not always been predictable or safe.
Researchers at Northwestern University may have found a way to affect the differentiation process. Using a process called scanning probe lithography, a well-understood technique that can trace three-dimensional microscopic shapes and reproduce them on flat surfaces, these researchers believe they can significantly influence the differentiation process.
In their studies, once these researchers reproduced specific patterns through this use of nanotechnology, they then introduced stem cells onto the patterned surface. This influenced the cells to differentiate into bone cells.
Your body has specialized cells called mesenchymal stem cells that are put into play when you need a repair of some kind. These cells are circulated in the blood and literally go to where they are needed. There, they differentiate into the kind of cells needed for the repair. This differentiation is partially based on the molecular structure of the cells around the needed repair. The matrix structure that makes up the surrounding cells determines the softness or hardness of the differentiated cells.
This is the process that the researchers at Northwestern University mimicked. In the laboratory, they use the cellular matrix as a pattern to develop a nano-landscape on a small piece of glass. To build this pattern, a series of pyramid-like points that were a hundred-thousand times smaller than a pencil point and extremely sharp were used to construct the pattern, molecule by molecule.
The future use of such a tool would be to take a sample of pluripotent cells from a person, place them on a specific matrix to quickly differentiate them into selected cells, and then replace them in that person in order to develop or repair specific tissues.
Researchers say this process could eventually produce any specified type of cell virtually on demand.
CRISPR and Induced Pluripotent Stem Cells
The CRISPR (or clustered regularly-interspaced short palindromic repeats) technique could potentially be used to produce induced pluripotent stem cells. This technique was originally designed to edit DNA sequences by snipping out and replacing a DNA sequence using an enzyme.
Induced pluripotent stem cells have been chemically produced before by introducing four genes into adult cells. This previous technique was developed due to the controversy surrounding the use of embryonic stem cells which are pluripotent. Inserting these genes into mature adult cells, which are not pluripotent, changed them into pluripotent cells capable of differentiating into any other kind of cell.
Other than the controversy involving the use of embryonic cells, introducing large genes into other cells to induce them to become the pluripotent type of cell involves using more than one vector. A single vector is not sufficient to contain all four genes that are necessary for this process or to express all of the genes needed.
Making a change in the CRISPR technique solved this issue. Rather than using the DNA slicing function, the researchers added a transcriptional activation factor to the Cas9 protein aspect of the technique. This allowed them to activate transcription at a certain location on the genome. This is very different from introducing genes into the cells.
A significant benefit of this change relates to the safety of the changed pluripotent cell. Previously, introducing genes to induce the changes could result in significant carcinogenicity. Introducing foreign genes always carried the possibility of also introducing oncogenic factors into the reprogramming. The new technique does away with this safety issue because it is activating the transcription of genes already in the cells.
Another benefit of this research is that it allows multiple genes to be activated through a single gene delivery system. This use of the CRISPR technique allows for five or more genes to be activated through a single vector.
With the original method of inducing pluripotent cells, the inefficiency of the method may have left some epigenetic memory behind, thus making the reprogramming effort incomplete.
This new technique also allows researchers to observe the functions of altered genes in the context of diseases or to make corrections to defective genes in individual cells.
Use of this CRISPR technique at the Gladstone Institutes allowed researchers to modify skin cells from mice into stem cells. Two genes that are only expressed in stem cells and that are necessary for pluripotency were targeted. These genes were Sox2 and Oct4. The function of these genes is to activate other stem cell genes and inhibit those of other cell types.
Either of these genes could be activated using the CRISPR technique. Using a single location on the genome was sufficient to stimulate the natural chain reaction that ended in the reprogramming that changed the cell into an induced pluripotent stem cell.
In the original technique of introducing genes into the cell, thousands of locations on the genome were typically targeted, changing the expression of genes at each location. The new CRISPR technique makes the production of induced pluripotent stem cells much more efficient. This is a tremendous benefit for the use of these cells in medical applications.
The present and future use of stem cells in medical applications appears to be self-evident. They are and will continue to be very important. Their use in combating the effects of aging has been shown to be effective, particularly through mechanisms in the hypothalamus. They have uses in repairing damaged cells and potentially even growing new organs, and given the difficulty of finding organ donors, this could be incredibly helpful. The other uses of these cells for medicine and rehabilitation is limited only by researchers’ imagination. There are several possibilities for future ways researchers may be able to produce and harness stem cells, from converting other cells into stem cells, and from developing new technologies to produce the environment needed for stem cells to transform into the cells. The possibilities are endless.
© Copyright 2018 Michael Lam, M.D. All Rights Reserved.