Can you imagine a world where doctors have the power to replace dead, disease-causing cells with healthy ones produced in a laboratory? With continued research into cell reprogramming that future isn’t far off. There have already been several successful trials with this technology. Despite its immense potential and expanding use, many individuals still remain unfamiliar with the concept of cell reprogramming.
So, what is cell reprogramming? And what are some of the obstacles that the field faces today? In this quick summary of cell reprogramming, we’ll answer these questions and more.
Cell Reprogramming vs. Direct Cell Reprogramming
First, let’s clarify the difference between cell reprogramming (sometimes called indirect cell reprogramming) and direct cell reprogramming. While the terms sound and look very similar, there is an important distinction.
Cell reprogramming is the act of reverting mature, specialised cells into induced pluripotent stem cells, also known as iPS cells. This process requires a stem or progenitor cell intermediary.
In contrast, direct cell reprogramming is defined as in vitro (laboratory) reprogramming of somatic cells into other cell types without the need for an intermediate pluripotent state.
Another term for direct cell reprogramming is transdifferentiation, which is the direct conversion of one differentiated cell type into another. Thus, the difference between these two types is whether they are direct or indirect – that is, involving an intermediary. (If you want to learn more about the rise of direct cell reprogramming, then read our full coverage of the topic here.)
What Is the Process of Cell Reprogramming?
To understand the process of cell reprogramming you first must understand the value of a pluripotent stem cell. These types of cells can self-renew through division.
Pluripotent cells then transform into one of the three early embryonic germ cell layers. In an adult body, these layers could potentially produce any cell or tissue that the body needs to repair itself.
The medical potential of pluripotent cells is huge, but until recently it was thought that embryonic stem cells (ESCs) were the only way to obtain them. That is until 2006 when Kazutoshi Takahashi and Shinya Yamanaka made a breakthrough.
These individuals discovered that you could take skin cells and change them into ‘induced’ pluripotent stem cells, also known as induced pluripotent stem cells (iPS cells).
This type is exciting because it offers some of the disease curing potential of embryonic stem cells while avoiding the moral issues that come with the ESCs.
You see, the only way to create these ESC lines is through destroying embryos, pre-implanted at the blastocyst stage. Even though the embryo only consists of 100–200 cells at this stage, it goes against the morals of people who believe that life begins at conception.
Embryonic stem cells can also trigger an immune rejection from their host. iPS cells would be a solution to these problems. The come from somatic cells and, when recovered from a human donor, they present a far lower risk of immune reaction.
Researchers are currently investigating how to best use the iPS cells to replace the cell loss caused by diseases. A common method involves injecting the genes Sox2, Oct4, Klf4, and cMyc into the cells through viruses, although other methods exist.
However, despite its names, the cells aren’t completely reprogrammed. ESCs and iPS cells still function differently and researchers are learning how to account for these differences.
‘In Vitro’ vs. ‘In Vivo’
There are currently two types: ‘in vitro’ and ‘in vivo’. For reference:
- In vitro means that an experiment or procedure is completed within a laboratory setting (outside of an animal or human).
- In vivo means that an experiment or procedure takes place within an living being, such as an animal or human.
‘In vitro’ is the primary method used for cell reprogramming. It involves using somatic cells from a blood, skin or bone marrow source. Somatic cells are differentiated cells other than reproductive cells.
Many commercial providers offer cell reprogramming services, such as Takara Bio, Axol Bio, Fujifilm CDI, REPROCELL (Stemgent), and numerous others.
These somatic cells are then reprogrammed into multipotent cells that fit the condition or illness they’re fighting. The key to success with this method often involves using the cell subtypes that are the most relevant cells to reprogram.
So, if someone had a heart disease, it might be logical to program it into a cardiac stem cell. Complete genetic manipulation and viral vectors have not had as much success in changing the gene pattern.
However, a second method is being investigated that uses chemicals to start cell reprogramming. The method is known as ‘in vivo’ and involves giving drugs to living patients.
This method of cell-lineage reprogramming is causing some excitement because it represents a more affordable solution. Unfortunately, it’s also very difficult to target one system in the body without affecting the others.
This presents safety problems because it could potentially affect any or all of the cells within the body. As such, a safe ‘in vivo’ solution for cell reprogramming is still many years off.
The Future of Cell Reprogramming
Different types of reprogramming can result in producing undifferentiated cells with varying degree of “stemness”. Technically, somatic cell nuclear transfer (SCNT) is the only method that can reprogram a somatic cell to a totipotent cell capable of creating a complete organism.
However, as described above, cellular reprogramming methods usually involve induced pluripotency via in vivo or in vitro manipulation.
Today, the main problems standing in the way of widespread iPS cell reprogramming are safety and cost.
Finding a way to produce iPS cells that are a near “biological equivalent” to embryonic stem cells is of interest to the research community because this would allow iPS cells to be created from patients for immediate use in transplantation.
For many medical conditions, this is a difficult goal, because a patient’s cells have often been affected by their own disease. However, accomplishing this could remove the need for immunosuppressive drugs and eliminate the rejection of transplanted cells.
Current methods are also too expensive for the general public, often costing hundreds of thousands of dollars or more per treatment.
Researchers are still a long way off from making both an affordable and effective treatment option. But, there’s still no shortage of interested parties in this new — potentially revolutionary — form of medicine.
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